Seminars in Immunopathology

, Volume 34, Issue 2, pp 281–297 | Cite as

Immunopathogenesis of Staphylococcus aureus pulmonary infection

Review

Abstract

Staphylococcus aureus is a common human pathogen highly evolved as both a component of the commensal flora and as a major cause of invasive infection. Severe respiratory infection due to staphylococci has been increasing due to the prevalence of more virulent USA300 CA-MRSA strains in the general population. The ability of S. aureus to adapt to the milieu of the respiratory tract has facilitated its emergence as a respiratory pathogen. Its metabolic versatility, the ability to scavenge iron, coordinate gene expression, and the horizontal acquisition of useful genetic elements have all contributed to its success as a component of the respiratory flora, in hospitalized patients, as a complication of influenza and in normal hosts. The expression of surface adhesins facilitates its persistence in the airways. In addition, the highly sophisticated interactions of the multiple S. aureus virulence factors, particularly the α-hemolysin and protein A, with diverse immune effectors in the lung such as ADAM10, TNFR1, EGFR, immunoglobulin, and complement all contribute to the pathogenesis of staphylococcal pneumonia.

Keywords

Airway Lung Epithelial Staphylococcus aureus Virulence Signaling 

References

  1. 1.
    Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S et al (2007) Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA 298:1763–1771PubMedGoogle Scholar
  2. 2.
    Deleo FR, Otto M, Kreiswirth BN, Chambers HF (2010) Community-associated meticillin-resistant Staphylococcus aureus. Lancet 375:1557–1568PubMedGoogle Scholar
  3. 3.
    Montgomery CP, Boyle-Vavra S, Adem PV, Lee JC, Husain AN, Clasen J et al (2008) Comparison of virulence in community-associated methicillin-resistant Staphylococcus aureus pulsotypes USA300 and USA400 in a rat model of pneumonia. J Infect Dis 198:561–570PubMedGoogle Scholar
  4. 4.
    Oswald NC, Shooter RA, Curwen MP (1958) Pneumonia complicating Asian influenza. Br Med J 2:1305–1311PubMedGoogle Scholar
  5. 5.
    Hageman JC, Uyeki TM, Francis JS, Jernigan DB, Wheeler JG, Bridges CB et al (2006) Severe community-acquired pneumonia due to Staphylococcus aureus, 2003–04 influenza season. Emerg Infect Dis 12:894–899PubMedGoogle Scholar
  6. 6.
    McDougal LK, Steward CD, Killgore GE, Chaitram JM, McAllister SK, Tenover FC (2003) Pulsed-field gel electrophoresis typing of oxacillin-resistant Staphylococcus aureus isolates from the United States: establishing a national database. J Clin Microbiol 41:5113–5120PubMedGoogle Scholar
  7. 7.
    Centers for Disease Control and Prevention (2003) Outbreaks of community-associated methicillin-resistant Staphylococcus aureus skin infections—Los Angeles County, California, 2002–2003. MMWR Morb Mortal Wkly Rep 52:88Google Scholar
  8. 8.
    Begier EM, Frenette K, Barrett NL, Mshar P, Petit S, Boxrud DJ et al (2004) A high-morbidity outbreak of methicillin-resistant Staphylococcus aureus among players on a college football team, facilitated by cosmetic body shaving and turf burns. Clin Infect Dis 39:1446–1453PubMedGoogle Scholar
  9. 9.
    Kazakova SV, Hageman JC, Matava M, Srinivasan A, Phelan L, Garfinkel B et al (2005) A clone of methicillin-resistant Staphylococcus aureus among professional football players. N Engl J Med 352:468–475PubMedGoogle Scholar
  10. 10.
    Gilbert M, MacDonald J, Gregson D, Siushansian J, Zhang K, Elsayed S et al (2006) Outbreak in Alberta of community-acquired (USA300) methicillin-resistant Staphylococcus aureus in people with a history of drug use, homelessness or incarceration. CMAJ 175:149–154PubMedGoogle Scholar
  11. 11.
    Centers for Disease Control and Prevention (2003) Methicillin-resistant Staphylococcus aureus infections in correctional facilities–Georgia, California, and Texas, 2001–2003. MMWR Morb Mortal Wkly Rep 52:992–996Google Scholar
  12. 12.
    Carrillo-Marquez MA, Hulten KG, Hammerman W, Lamberth L, Mason EO, Kaplan SL (2011) Staphylococcus aureus pneumonia in children in the era of community-acquired methicillin-resistance at Texas Children’s Hospital. Pediatr Infect Dis J 30:545–550PubMedGoogle Scholar
  13. 13.
    Herold BC, Immergluck LC, Maranan MC, Lauderdale DS, Gaskin RE, Boyle-Vavra S et al (1998) Community-acquired methicillin-resistant Staphylococcus aureus in children with no identified predisposing risk. JAMA 279:593–598PubMedGoogle Scholar
  14. 14.
    Boucher HW, Corey GR (2008) Epidemiology of methicillin-resistant Staphylococcus aureus. Clin Infect Dis 46(Suppl 5):S344–S349PubMedGoogle Scholar
  15. 15.
    Finelli L, Fiore A, Dhara R, Brammer L, Shay DK, Kamimoto L et al (2008) Influenza-associated pediatric mortality in the United States: increase of Staphylococcus aureus coinfection. Pediatrics 122:805–811PubMedGoogle Scholar
  16. 16.
    Garnier F, Tristan A, Francois B, Etienne J, Delage-Corre M, Martin C et al (2006) Pneumonia and new methicillin-resistant Staphylococcus aureus clone. Emerg Infect Dis 12:498–500PubMedGoogle Scholar
  17. 17.
    Risson DC, O’Connor ED, Guard RW, Schooneveldt JM, Nimmo GR (2007) A fatal case of necrotising pneumonia due to community-associated methicillin-resistant Staphylococcus aureus. Med J Aust 186:479–480PubMedGoogle Scholar
  18. 18.
    Iverson AR, Boyd KL, McAuley JL, Plano LR, Hart ME, McCullers JA (2011) Influenza virus primes mice for pneumonia from Staphylococcus aureus. J Infect Dis 203:880–888PubMedGoogle Scholar
  19. 19.
    Li M, Diep BA, Villaruz AE, Braughton KR, Jiang X, DeLeo FR et al (2009) Evolution of virulence in epidemic community-associated methicillin-resistant Staphylococcus aureus. Proc Natl Acad Sci USA 106:5883–5888PubMedGoogle Scholar
  20. 20.
    Diep BA, Gill SR, Chang RF, Phan TH, Chen JH, Davidson MG et al (2006) Complete genome sequence of USA300, an epidemic clone of community-acquired meticillin-resistant Staphylococcus aureus. Lancet 367:731–739PubMedGoogle Scholar
  21. 21.
    Diep BA, Carleton HA, Chang RF, Sensabaugh GF, Perdreau-Remington F (2006) Roles of 34 virulence genes in the evolution of hospital- and community-associated strains of methicillin-resistant Staphylococcus aureus. J Infect Dis 193:1495–1503PubMedGoogle Scholar
  22. 22.
    Diep BA, Stone GG, Basuino L, Graber CJ, Miller A, des Etages SA et al (2008) The arginine catabolic mobile element and staphylococcal chromosomal cassette mec linkage: convergence of virulence and resistance in the USA300 clone of methicillin-resistant Staphylococcus aureus. J Infect Dis 197:1523–1530PubMedGoogle Scholar
  23. 23.
    Montgomery CP, Boyle-Vavra S, Daum RS (2009) The arginine catabolic mobile element is not associated with enhanced virulence in experimental invasive disease caused by the community-associated methicillin-resistant Staphylococcus aureus USA300 genetic background. Infect Immun 77:2650–2656PubMedGoogle Scholar
  24. 24.
    Diep BA, Otto M (2008) The role of virulence determinants in community-associated MRSA pathogenesis. Trends Microbiol 16:361–369PubMedGoogle Scholar
  25. 25.
    Bubeck Wardenburg J, Patel RJ, Schneewind O (2007) Surface proteins and exotoxins are required for the pathogenesis of Staphylococcus aureus pneumonia. Infect Immun 75:1040–1044PubMedGoogle Scholar
  26. 26.
    Bubeck Wardenburg J, Bae T, Otto M, Deleo FR, Schneewind O (2007) Poring over pores: alpha-hemolysin and Panton–Valentine leukocidin in Staphylococcus aureus pneumonia. Nat Med 13:1405–1406PubMedGoogle Scholar
  27. 27.
    Bartlett AH, Foster TJ, Hayashida A, Park PW (2008) Alpha-toxin facilitates the generation of CXC chemokine gradients and stimulates neutrophil homing in Staphylococcus aureus pneumonia. J Infect Dis 198:1529–1535PubMedGoogle Scholar
  28. 28.
    Pishchany G, McCoy AL, Torres VJ, Krause JC, Crowe JE Jr, Fabry ME et al (2010) Specificity for human hemoglobin enhances Staphylococcus aureus infection. Cell Host Microbe 8:544–550PubMedGoogle Scholar
  29. 29.
    Otto M (2011) A MRSA-terious enemy among us: end of the PVL controversy? Nat Med 17:169–170PubMedGoogle Scholar
  30. 30.
    Kapral FA, Shayegani MG (1959) Intracellular survival of staphylococci. J Exp Med 110:123–138PubMedGoogle Scholar
  31. 31.
    Melly MA, Thomison JB, Rogers DE (1960) Fate of staphylococci within human leukocytes. J Exp Med 112:1121–1130PubMedGoogle Scholar
  32. 32.
    da Silva MC, Zahm JM, Gras D, Bajolet O, Abely M, Hinnrasky J et al (2004) Dynamic interaction between airway epithelial cells and Staphylococcus aureus. Am J Physiol Lung Cell Mol Physiol 287:L543–L551PubMedGoogle Scholar
  33. 33.
    Belay N, Rasooly A (2002) Staphylococcus aureus growth and enterotoxin A production in an anaerobic environment. J Food Prot 65:199–204PubMedGoogle Scholar
  34. 34.
    Recsei P, Kreiswirth B, O’Reilly M, Schlievert P, Gruss A, Novick RP (1986) Regulation of exoprotein gene expression in Staphylococcus aureus by agar. Mol Gen Genet 202:58–61PubMedGoogle Scholar
  35. 35.
    Novick RP (2003) Autoinduction and signal transduction in the regulation of staphylococcal virulence. Mol Microbiol 48:1429–1449PubMedGoogle Scholar
  36. 36.
    Cheung GY, Wang R, Khan BA, Sturdevant DE, Otto M (2011) Role of the accessory gene regulator agr in community-associated methicillin-resistant Staphylococcus aureus pathogenesis. Infect Immun 79:1927–1935PubMedGoogle Scholar
  37. 37.
    Traber KE, Lee E, Benson S, Corrigan R, Cantera M, Shopsin B et al (2008) agr function in clinical Staphylococcus aureus isolates. Microbiology 154:2265–2274PubMedGoogle Scholar
  38. 38.
    Heyer G, Saba S, Adamo R, Rush W, Soong G, Cheung A et al (2002) Staphylococcus aureus agr and sarA functions are required for invasive infection but not inflammatory responses in the lung. Infect Immun 70:127–133PubMedGoogle Scholar
  39. 39.
    Montgomery CP, Boyle-Vavra S, Daum RS (2010) Importance of the global regulators Agr and SaeRS in the pathogenesis of CA-MRSA USA300 infection. PLoS One 5:e15177PubMedGoogle Scholar
  40. 40.
    Qazi SN, Counil E, Morrissey J, Rees CE, Cockayne A, Winzer K et al (2001) agr expression precedes escape of internalized Staphylococcus aureus from the host endosome. Infect Immun 69:7074–7082PubMedGoogle Scholar
  41. 41.
    Shompole S, Henon KT, Liou LE, Dziewanowska K, Bohach GA, Bayles KW (2003) Biphasic intracellular expression of Staphylococcus aureus virulence factors and evidence for Agr-mediated diffusion sensing. Mol Microbiol 49:919–927PubMedGoogle Scholar
  42. 42.
    Giese B, Glowinski F, Paprotka K, Dittmann S, Steiner T, Sinha B et al (2011) Expression of delta-toxin by Staphylococcus aureus mediates escape from phago-endosomes of human epithelial and endothelial cells in the presence of beta-toxin. Cell Microbiol 13:316–329PubMedGoogle Scholar
  43. 43.
    Jarry TM, Cheung AL (2006) Staphylococcus aureus escapes more efficiently from the phagosome of a cystic fibrosis bronchial epithelial cell line than from its normal counterpart. Infect Immun 74:2568–2577PubMedGoogle Scholar
  44. 44.
    Bayles KW, Wesson CA, Liou LE, Fox LK, Bohach GA, Trumble WR (1998) Intracellular Staphylococcus aureus escapes the endosome and induces apoptosis in epithelial cells. Infect Immun 66:336–342PubMedGoogle Scholar
  45. 45.
    Kubica M, Guzik K, Koziel J, Zarebski M, Richter W, Gajkowska B et al (2008) A potential new pathway for Staphylococcus aureus dissemination: the silent survival of S. aureus phagocytosed by human monocyte-derived macrophages. PLoS One 3:e1409PubMedGoogle Scholar
  46. 46.
    Gresham HD, Lowrance JH, Caver TE, Wilson BS, Cheung AL, Lindberg FP (2000) Survival of Staphylococcus aureus inside neutrophils contributes to infection. J Immunol 164:3713–3722PubMedGoogle Scholar
  47. 47.
    Voyich JM, Braughton KR, Sturdevant DE, Whitney AR, Said-Salim B, Porcella SF et al (2005) Insights into mechanisms used by Staphylococcus aureus to avoid destruction by human neutrophils. J Immunol 175:3907–3919PubMedGoogle Scholar
  48. 48.
    Konetschny-Rapp S, Jung G, Meiwes J, Zahner H, Staphyloferrin A (1990) A structurally new siderophore from staphylococci. Eur J Biochem 191:65–74PubMedGoogle Scholar
  49. 49.
    Courcol RJ, Trivier D, Bissinger MC, Martin GR, Brown MR (1997) Siderophore production by Staphylococcus aureus and identification of iron-regulated proteins. Infect Immun 65:1944–1948PubMedGoogle Scholar
  50. 50.
    Dale SE, Doherty-Kirby A, Lajoie G, Heinrichs DE (2004) Role of siderophore biosynthesis in virulence of Staphylococcus aureus: identification and characterization of genes involved in production of a siderophore. Infect Immun 72:29–37PubMedGoogle Scholar
  51. 51.
    Torres VJ, Pishchany G, Humayun M, Schneewind O, Skaar EP (2006) Staphylococcus aureus IsdB is a hemoglobin receptor required for heme iron utilization. J Bacteriol 188:8421–8429PubMedGoogle Scholar
  52. 52.
    Beasley FC, Marolda CL, Cheung J, Buac S, Heinrichs DE (2011) Staphylococcus aureus transporters Hts, Sir, and Sst capture iron liberated from human transferrin by Staphyloferrin A, Staphyloferrin B, and catecholamine stress hormones, respectively, and contribute to virulence. Infect Immun 79:2345–2355PubMedGoogle Scholar
  53. 53.
    Torres VJ, Attia AS, Mason WJ, Hood MI, Corbin BD, Beasley FC et al (2010) Staphylococcus aureus fur regulates the expression of virulence factors that contribute to the pathogenesis of pneumonia. Infect Immun 78:1618–1628PubMedGoogle Scholar
  54. 54.
    Datta R, Huang SS (2008) Risk of infection and death due to methicillin-resistant Staphylococcus aureus in long-term carriers. Clin Infect Dis 47:176–181PubMedGoogle Scholar
  55. 55.
    Lederer SR, Riedelsdorf G, Schiffl H (2007) Nasal carriage of meticillin resistant Staphylococcus aureus: the prevalence, patients at risk and the effect of elimination on outcomes among outclinic haemodialysis patients. Eur J Med Res 12:284–288PubMedGoogle Scholar
  56. 56.
    Diller R, Sonntag AK, Mellmann A, Grevener K, Senninger N, Kipp F et al (2008) Evidence for cost reduction based on pre-admission MRSA screening in general surgery. Int J Hyg Environ Health 211:205–212PubMedGoogle Scholar
  57. 57.
    Patti JM, Allen BL, McGavin MJ, Hook M (1994) MSCRAMM-mediated adherence of microorganisms to host tissues. Annu Rev Microbiol 48:585–617PubMedGoogle Scholar
  58. 58.
    Hienz SA, Schennings T, Heimdahl A, Flock JI (1996) Collagen binding of Staphylococcus aureus is a virulence factor in experimental endocarditis. J Infect Dis 174:83–88PubMedGoogle Scholar
  59. 59.
    Rhem MN, Lech EM, Patti JM, McDevitt D, Hook M, Jones DB et al (2000) The collagen-binding adhesin is a virulence factor in Staphylococcus aureus keratitis. Infect Immun 68:3776–3779PubMedGoogle Scholar
  60. 60.
    de Bentzmann S, Tristan A, Etienne J, Brousse N, Vandenesch F, Lina G (2004) Staphylococcus aureus isolates associated with necrotizing pneumonia bind to basement membrane type I and IV collagens and laminin. J Infect Dis 190:1506–1515PubMedGoogle Scholar
  61. 61.
    Mongodin E, Bajolet O, Cutrona J, Bonnet N, Dupuit F, Puchelle E et al (2002) Fibronectin-binding proteins of Staphylococcus aureus are involved in adherence to human airway epithelium. Infect Immun 70:620–630PubMedGoogle Scholar
  62. 62.
    Schaffer AC, Solinga RM, Cocchiaro J, Portoles M, Kiser KB, Risley A et al (2006) Immunization with Staphylococcus aureus clumping factor B, a major determinant in nasal carriage, reduces nasal colonization in a murine model. Infect Immun 74:2145–2153PubMedGoogle Scholar
  63. 63.
    McElroy MC, Cain DJ, Tyrrell C, Foster TJ, Haslett C (2002) Increased virulence of a fibronectin-binding protein mutant of Staphylococcus aureus in a rat model of pneumonia. Infect Immun 70:3865–3873PubMedGoogle Scholar
  64. 64.
    Higgins J, Loughman A, van Kessel KP, van Strijp JA, Foster TJ (2006) Clumping factor A of Staphylococcus aureus inhibits phagocytosis by human polymorphonuclear leucocytes. FEMS Microbiol Lett 258:290–296PubMedGoogle Scholar
  65. 65.
    Palmqvist N, Patti JM, Tarkowski A, Josefsson E (2004) Expression of staphylococcal clumping factor A impedes macrophage phagocytosis. Microbes Infect 6:188–195PubMedGoogle Scholar
  66. 66.
    Josefsson E, Hartford O, O’Brien L, Patti JM, Foster T (2001) Protection against experimental Staphylococcus aureus arthritis by vaccination with clumping factor A, a novel virulence determinant. J Infect Dis 184:1572–1580PubMedGoogle Scholar
  67. 67.
    Vernachio J, Bayer AS, Le T, Chai YL, Prater B, Schneider A et al (2003) Anti-clumping factor A immunoglobulin reduces the duration of methicillin-resistant Staphylococcus aureus bacteremia in an experimental model of infective endocarditis. Antimicrob Agents Chemother 47:3400–3406PubMedGoogle Scholar
  68. 68.
    Moreillon P, Entenza JM, Francioli P, McDevitt D, Foster TJ, Francois P et al (1995) Role of Staphylococcus aureus coagulase and clumping factor in pathogenesis of experimental endocarditis. Infect Immun 63:4738–4743PubMedGoogle Scholar
  69. 69.
    Weems JJ Jr, Steinberg JP, Filler S, Baddley JW, Corey GR, Sampathkumar P et al (2006) Phase II, randomized, double-blind, multicenter study comparing the safety and pharmacokinetics of tefibazumab to placebo for treatment of Staphylococcus aureus bacteremia. Antimicrob Agents Chemother 50:2751–2755PubMedGoogle Scholar
  70. 70.
    O’Brien LM, Walsh EJ, Massey RC, Peacock SJ, Foster TJ (2002) Staphylococcus aureus clumping factor B (ClfB) promotes adherence to human type I cytokeratin 10: implications for nasal colonization. Cell Microbiol 4:759–770PubMedGoogle Scholar
  71. 71.
    Mazmanian SK, Liu G, Ton-That H, Schneewind O (1999) Staphylococcus aureus sortase, an enzyme that anchors surface proteins to the cell wall. Science 285:760–763PubMedGoogle Scholar
  72. 72.
    Wertheim HF, Walsh E, Choudhurry R, Melles DC, Boelens HA, Miajlovic H et al (2008) Key role for clumping factor B in Staphylococcus aureus nasal colonization of humans. PLoS Med 5:e17PubMedGoogle Scholar
  73. 73.
    Song L, Hobaugh MR, Shustak C, Cheley S, Bayley H, Gouaux JE (1996) Structure of staphylococcal alpha-hemolysin, a heptameric transmembrane pore. Science 274:1859–1866PubMedGoogle Scholar
  74. 74.
    Burlak C, Hammer CH, Robinson MA, Whitney AR, McGavin MJ, Kreiswirth BN et al (2007) Global analysis of community-associated methicillin-resistant Staphylococcus aureus exoproteins reveals molecules produced in vitro and during infection. Cell Microbiol 9:1172–1190PubMedGoogle Scholar
  75. 75.
    Yun YS, Min YG, Rhee CS, Jung IH, Koh YY, Jang TY et al (1999) Effects of alpha-toxin of Staphylococcus aureus on the ciliary activity and ultrastructure of human nasal ciliated epithelial cells. Laryngoscope 109:2021–2024PubMedGoogle Scholar
  76. 76.
    Rose F, Dahlem G, Guthmann B, Grimminger F, Maus U, Hanze J et al (2002) Mediator generation and signaling events in alveolar epithelial cells attacked by S. aureus alpha-toxin. Am J Physiol Lung Cell Mol Physiol 282:L207–L214PubMedGoogle Scholar
  77. 77.
    Wilke GA, Bubeck Wardenburg J (2010) Role of a disintegrin and metalloprotease 10 in Staphylococcus aureus alpha-hemolysin-mediated cellular injury. Proc Natl Acad Sci USA 107:13473–13478PubMedGoogle Scholar
  78. 78.
    Seeger W, Birkemeyer RG, Ermert L, Suttorp N, Bhakdi S, Duncker HR (1990) Staphylococcal alpha-toxin-induced vascular leakage in isolated perfused rabbit lungs. Lab Invest 63:341–349PubMedGoogle Scholar
  79. 79.
    Phillips JR, Tripp TJ, Regelmann WE, Schlievert PM, Wangensteen OD (2006) Staphylococcal alpha-toxin causes increased tracheal epithelial permeability. Pediatr Pulmonol 41:1146–1152PubMedGoogle Scholar
  80. 80.
    McElroy MC, Harty HR, Hosford GE, Boylan GM, Pittet JF, Foster TJ (1999) Alpha-toxin damages the air–blood barrier of the lung in a rat model of Staphylococcus aureus-induced pneumonia. Infect Immun 67:5541–5544PubMedGoogle Scholar
  81. 81.
    Bantel H, Sinha B, Domschke W, Peters G, Schulze-Osthoff K, Janicke RU (2001) alpha-Toxin is a mediator of Staphylococcus aureus-induced cell death and activates caspases via the intrinsic death pathway independently of death receptor signaling. J Cell Biol 155:637–648PubMedGoogle Scholar
  82. 82.
    Jonas D, Walev I, Berger T, Liebetrau M, Palmer M, Bhakdi S (1994) Novel path to apoptosis: small transmembrane pores created by staphylococcal alpha-toxin in T lymphocytes evoke internucleosomal DNA degradation. Infect Immun 62:1304–1312PubMedGoogle Scholar
  83. 83.
    Craven RR, Gao X, Allen IC, Gris D, Bubeck Wardenburg J, McElvania-Tekippe E et al (2009) Staphylococcus aureus alpha-hemolysin activates the NLRP3-inflammasome in human and mouse monocytic cells. PLoS One 4:e7446PubMedGoogle Scholar
  84. 84.
    Munoz-Planillo R, Franchi L, Miller LS, Nunez G (2009) A critical role for hemolysins and bacterial lipoproteins in Staphylococcus aureus-induced activation of the Nlrp3 inflammasome. J Immunol 183:3942–3948PubMedGoogle Scholar
  85. 85.
    Grimminger F, Rose F, Sibelius U, Meinhardt M, Potzsch B, Spriestersbach R et al (1997) Human endothelial cell activation and mediator release in response to the bacterial exotoxins Escherichia coli hemolysin and staphylococcal alpha-toxin. J Immunol 159:1909–1916PubMedGoogle Scholar
  86. 86.
    Liang X, Ji Y (2007) Involvement of alpha5beta1-integrin and TNF-alpha in Staphylococcus aureus alpha-toxin-induced death of epithelial cells. Cell Microbiol 9:1809–1821PubMedGoogle Scholar
  87. 87.
    Bubeck Wardenburg J, Schneewind O (2008) Vaccine protection against Staphylococcus aureus pneumonia. J Exp Med 205:287–294PubMedGoogle Scholar
  88. 88.
    Ragle BE, Bubeck Wardenburg J (2009) Anti-alpha-hemolysin monoclonal antibodies mediate protection against Staphylococcus aureus pneumonia. Infect Immun 77:2712–2718PubMedGoogle Scholar
  89. 89.
    Ragle BE, Karginov VA, Bubeck Wardenburg J (2010) Prevention and treatment of Staphylococcus aureus pneumonia with a beta-cyclodextrin derivative. Antimicrob Agents Chemother 54:298–304PubMedGoogle Scholar
  90. 90.
    Aarestrup FM, Larsen HD, Eriksen NH, Elsberg CS, Jensen NE (1999) Frequency of alpha- and beta-haemolysin in Staphylococcus aureus of bovine and human origin. A comparison between pheno- and genotype and variation in phenotypic expression. APMIS 107:425–430PubMedGoogle Scholar
  91. 91.
    Doery HM, Magnusson BJ, Cheyne IM, Sulasekharam J (1963) A phospholipase in staphylococcal toxin which hydrolyses sphingomyelin. Nature 198:1091–1092PubMedGoogle Scholar
  92. 92.
    Marshall MJ, Bohach GA, Boehm DF (2000) Characterization of Staphylococcus aureus beta-toxin induced leukotoxicity. J Nat Toxins 9:125–138PubMedGoogle Scholar
  93. 93.
    Walev I, Weller U, Strauch S, Foster T, Bhakdi S (1996) Selective killing of human monocytes and cytokine release provoked by sphingomyelinase (beta-toxin) of Staphylococcus aureus. Infect Immun 64:2974–2979PubMedGoogle Scholar
  94. 94.
    Huseby M, Shi K, Brown CK, Digre J, Mengistu F, Seo KS et al (2007) Structure and biological activities of beta toxin from Staphylococcus aureus. J Bacteriol 189:8719–8726PubMedGoogle Scholar
  95. 95.
    Kim CS, Jeon SY, Min YG, Rhyoo C, Kim JW, Yun JB et al (2000) Effects of beta-toxin of Staphylococcus aureus on ciliary activity of nasal epithelial cells. Laryngoscope 110:2085–2088PubMedGoogle Scholar
  96. 96.
    Hayashida A, Bartlett AH, Foster TJ, Park PW (2009) Staphylococcus aureus beta-toxin induces lung injury through syndecan-1. Am J Pathol 174:509–518PubMedGoogle Scholar
  97. 97.
    Mehlin C, Headley CM, Klebanoff SJ (1999) An inflammatory polypeptide complex from Staphylococcus epidermidis: isolation and characterization. J Exp Med 189:907–918PubMedGoogle Scholar
  98. 98.
    Wang R, Braughton KR, Kretschmer D, Bach TH, Queck SY, Li M et al (2007) Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA. Nat Med 13:1510–1514PubMedGoogle Scholar
  99. 99.
    Kretschmer D, Gleske AK, Rautenberg M, Wang R, Koberle M, Bohn E et al (2010) Human formyl peptide receptor 2 senses highly pathogenic Staphylococcus aureus. Cell Host Microbe 7:463–473PubMedGoogle Scholar
  100. 100.
    Queck SY, Khan BA, Wang R, Bach TH, Kretschmer D, Chen L et al (2009) Mobile genetic element-encoded cytolysin connects virulence to methicillin resistance in MRSA. PLoS Pathog 5:e1000533PubMedGoogle Scholar
  101. 101.
    Joo HS, Cheung GY, Otto M (2011) Antimicrobial activity of community-associated methicillin-resistant Staphylococcus aureus is caused by phenol-soluble modulin derivatives. J Biol Chem 286:8933–8940PubMedGoogle Scholar
  102. 102.
    Wang R, Khan BA, Cheung GY, Bach TH, Jameson-Lee M, Kong KF et al (2011) Staphylococcus epidermidis surfactant peptides promote biofilm maturation and dissemination of biofilm-associated infection in mice. J Clin Invest 121:238–248PubMedGoogle Scholar
  103. 103.
    Janzon L, Lofdahl S, Arvidson S (1989) Identification and nucleotide sequence of the delta-lysin gene, hld, adjacent to the accessory gene regulator (agr) of Staphylococcus aureus. Mol Gen Genet 219:480–485PubMedGoogle Scholar
  104. 104.
    Kreger AS, Kim KS, Zaboretzky F, Bernheimer AW (1971) Purification and properties of staphylococcal delta hemolysin. Infect Immun 3:449–465PubMedGoogle Scholar
  105. 105.
    Prevost G, Cribier B, Couppie P, Petiau P, Supersac G, Finck-Barbancon V et al (1995) Panton-Valentine leucocidin and gamma-hemolysin from Staphylococcus aureus ATCC 49775 are encoded by distinct genetic loci and have different biological activities. Infect Immun 63:4121–4129PubMedGoogle Scholar
  106. 106.
    Gladstone GP, Van Heyningen WE (1957) Staphylococcal leucocidins. Br J Exp Pathol 38:123–137PubMedGoogle Scholar
  107. 107.
    Gauduchon V, Werner S, Prevost G, Monteil H, Colin DA (2001) Flow cytometric determination of Panton–Valentine leucocidin S component binding. Infect Immun 69:2390–2395PubMedGoogle Scholar
  108. 108.
    Miles G, Movileanu L, Bayley H (2002) Subunit composition of a bicomponent toxin: staphylococcal leukocidin forms an octameric transmembrane pore. Protein Sci 11:894–902PubMedGoogle Scholar
  109. 109.
    Finck-Barbancon V, Duportail G, Meunier O, Colin DA (1993) Pore formation by a two-component leukocidin from Staphylococcus aureus within the membrane of human polymorphonuclear leukocytes. Biochim Biophys Acta 1182:275–282PubMedGoogle Scholar
  110. 110.
    Li M, Cheung GY, Hu J, Wang D, Joo HS, Deleo FR et al (2010) Comparative analysis of virulence and toxin expression of global community-associated methicillin-resistant Staphylococcus aureus strains. J Infect Dis 202:1866–1876PubMedGoogle Scholar
  111. 111.
    Loffler B, Hussain M, Grundmeier M, Bruck M, Holzinger D, Varga G et al (2010) Staphylococcus aureus Panton–Valentine leukocidin is a very potent cytotoxic factor for human neutrophils. PLoS Pathog 6:e1000715PubMedGoogle Scholar
  112. 112.
    Diep BA, Chan L, Tattevin P, Kajikawa O, Martin TR, Basuino L et al (2010) Polymorphonuclear leukocytes mediate Staphylococcus aureus Panton–Valentine leukocidin-induced lung inflammation and injury. Proc Natl Acad Sci USA 107:5587–5592PubMedGoogle Scholar
  113. 113.
    Genestier AL, Michallet MC, Prevost G, Bellot G, Chalabreysse L, Peyrol S et al (2005) Staphylococcus aureus Panton–Valentine leukocidin directly targets mitochondria and induces Bax-independent apoptosis of human neutrophils. J Clin Invest 115:3117–3127PubMedGoogle Scholar
  114. 114.
    Zivkovic A, Sharif O, Stich K, Doninger B, Biaggio M, Colinge J et al (2011) TLR 2 and CD14 mediate innate immunity and lung inflammation to staphylococcal Panton–Valentine leukocidin in vivo. J Immunol 186:1608–1617PubMedGoogle Scholar
  115. 115.
    Ward PD, Turner WH (1980) Identification of staphylococcal Panton–Valentine leukocidin as a potent dermonecrotic toxin. Infect Immun 28:393–397PubMedGoogle Scholar
  116. 116.
    Lina G, Piemont Y, Godail-Gamot F, Bes M, Peter MO, Gauduchon V et al (1999) Involvement of Panton–Valentine leukocidin-producing Staphylococcus aureus in primary skin infections and pneumonia. Clin Infect Dis 29:1128–1132PubMedGoogle Scholar
  117. 117.
    Francis JS, Doherty MC, Lopatin U, Johnston CP, Sinha G, Ross T et al (2005) Severe community-onset pneumonia in healthy adults caused by methicillin-resistant Staphylococcus aureus carrying the Panton–Valentine leukocidin genes. Clin Infect Dis 40:100–107PubMedGoogle Scholar
  118. 118.
    Gillet Y, Issartel B, Vanhems P, Fournet JC, Lina G, Bes M et al (2002) Association between Staphylococcus aureus strains carrying gene for Panton–Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients. Lancet 359:753–759PubMedGoogle Scholar
  119. 119.
    Vardakas KZ, Matthaiou DK, Falagas ME (2009) Incidence, characteristics and outcomes of patients with severe community acquired-MRSA pneumonia. Eur Respir J 34:1148–1158PubMedGoogle Scholar
  120. 120.
    Labandeira-Rey M, Couzon F, Boisset S, Brown EL, Bes M, Benito Y et al (2007) Staphylococcus aureus Panton–Valentine leukocidin causes necrotizing pneumonia. Science 315:1130–1133PubMedGoogle Scholar
  121. 121.
    Brown EL, Dumitrescu O, Thomas D, Badiou C, Koers EM, Choudhury P et al (2009) The Panton–Valentine leukocidin vaccine protects mice against lung and skin infections caused by Staphylococcus aureus USA300. Clin Microbiol Infect 15:156–164Google Scholar
  122. 122.
    Vandenesch F, Couzon F, Boisset S, Benito Y, Brown EL, Lina G et al (2010) The Panton–Valentine leukocidin is a virulence factor in a murine model of necrotizing pneumonia. J Infect Dis 201:967–969, author reply 969–970PubMedGoogle Scholar
  123. 123.
    Villaruz AE, Bubeck Wardenburg J, Khan BA, Whitney AR, Sturdevant DE, Gardner DJ et al (2009) A point mutation in the agr locus rather than expression of the Panton–Valentine leukocidin caused previously reported phenotypes in Staphylococcus aureus pneumonia and gene regulation. J Infect Dis 200:724–734PubMedGoogle Scholar
  124. 124.
    Mollick JA, McMasters RL, Grossman D, Rich RR (1993) Localization of a site on bacterial superantigens that determines T cell receptor beta chain specificity. J Exp Med 177:283–293PubMedGoogle Scholar
  125. 125.
    Li H, Llera A, Malchiodi EL, Mariuzza RA (1999) The structural basis of T cell activation by superantigens. Annu Rev Immunol 17:435–466PubMedGoogle Scholar
  126. 126.
    Marrack P, Kappler J (1990) The staphylococcal enterotoxins and their relatives. Science 248:705–711PubMedGoogle Scholar
  127. 127.
    Lambris JD, Ricklin D, Geisbrecht BV (2008) Complement evasion by human pathogens. Nat Rev Microbiol 6:132–142PubMedGoogle Scholar
  128. 128.
    Bekeredjian-Ding I, Inamura S, Giese T, Moll H, Endres S, Sing A et al (2007) Staphylococcus aureus protein A triggers T cell-independent B cell proliferation by sensitizing B cells for TLR2 ligands. J Immunol 178:2803–2812PubMedGoogle Scholar
  129. 129.
    Silverman GJ, Nayak JV, Warnatz K, Hajjar FF, Cary S, Tighe H et al (1998) The dual phases of the response to neonatal exposure to a VH family-restricted staphylococcal B cell superantigen. J Immunol 161:5720–5732PubMedGoogle Scholar
  130. 130.
    Smith EJ, Visai L, Kerrigan SW, Speziale P, Foster TJ (2011) The Sbi protein: a multifunctional immune evasion factor of Staphylococcus aureus. Infect Immun 79:3801–3809PubMedGoogle Scholar
  131. 131.
    Moks T, Abrahmsen L, Nilsson B, Hellman U, Sjoquist J, Uhlen M (1986) Staphylococcal protein A consists of five IgG-binding domains. Eur J Biochem 156:637–643PubMedGoogle Scholar
  132. 132.
    Uhlen M, Guss B, Nilsson B, Gatenbeck S, Philipson L, Lindberg M (1984) Complete sequence of the staphylococcal gene encoding protein A. A gene evolved through multiple duplications. J Biol Chem 259:1695–1702PubMedGoogle Scholar
  133. 133.
    Rajagopalan G, Sen MM, Singh M, Murali NS, Nath KA, Iijima K et al (2006) Intranasal exposure to staphylococcal enterotoxin B elicits an acute systemic inflammatory response. Shock 25:647–656PubMedGoogle Scholar
  134. 134.
    Zen K, Masuda J, Ogata J (1996) Monocyte-derived macrophages prime peripheral T cells to undergo apoptosis by cell–cell contact via ICAM-1/LFA-1-dependent mechanism. Immunobiology 195:323–333PubMedGoogle Scholar
  135. 135.
    Miller EJ, Nagao S, Carr FK, Noble JM, Cohen AB (1996) Interleukin-8 (IL-8) is a major neutrophil chemotaxin from human alveolar macrophages stimulated with staphylococcal enterotoxin A (SEA). Inflamm Res 45:386–392PubMedGoogle Scholar
  136. 136.
    Fuller AF Jr, Swartz MN, Wolfson JS, Salzman R (1980) Toxic-shock syndrome. N Engl J Med 303:881PubMedGoogle Scholar
  137. 137.
    Shands KN, Schmid GP, Dan BB, Blum D, Guidotti RJ, Hargrett NT et al (1980) Toxic-shock syndrome in menstruating women: association with tampon use and Staphylococcus aureus and clinical features in 52 cases. N Engl J Med 303:1436–1442PubMedGoogle Scholar
  138. 138.
    Osterholm MT, Davis JP, Gibson RW, Forfang JC, Stolz SJ, Vergeront JM (1982) Toxic shock syndrome: relation to catamenial products, personal health and hygiene, and sexual practices. Ann Intern Med 96:954–958PubMedGoogle Scholar
  139. 139.
    Reingold AL, Dan BB, Shands KN, Broome CV (1982) Toxic-shock syndrome not associated with menstruation. A review of 54 cases. Lancet 1:1–4PubMedGoogle Scholar
  140. 140.
    Wilkins EG, Nye F, Roberts C, de Saxe M (1985) Probable toxic shock syndrome with primary staphylococcal pneumonia. J Infect 11:231–232PubMedGoogle Scholar
  141. 141.
    MacDonald KL, Osterholm MT, Hedberg CW, Schrock CG, Peterson GF, Jentzen JM et al (1987) Toxic shock syndrome. A newly recognized complication of influenza and influenzalike illness. JAMA 257:1053–1058PubMedGoogle Scholar
  142. 142.
    Hirsch B, Stair T, Horowitz BZ, Brooks C (1984) Toxic shock syndrome from staphylococcal pharyngitis. Ear Nose Throat J 63:494–497PubMedGoogle Scholar
  143. 143.
    Dann EJ, Weinberger M, Gillis S, Parsonnet J, Shapiro M, Moses AE (1994) Bacterial laryngotracheitis associated with toxic shock syndrome in an adult. Clin Infect Dis 18:437–439PubMedGoogle Scholar
  144. 144.
    Zhang WJ, Sarawar S, Nguyen P, Daly K, Rehg JE, Doherty PC et al (1996) Lethal synergism between influenza infection and staphylococcal enterotoxin B in mice. J Immunol 157:5049–5060PubMedGoogle Scholar
  145. 145.
    Dinges MM, Orwin PM, Schlievert PM (2000) Exotoxins of Staphylococcus aureus. Clin Microbiol Rev 13:16–34 (table of contents)PubMedGoogle Scholar
  146. 146.
    Martin WJ, Marcus S (1964) Relation of pyrogenic and emetic properties of enterobacteriaceal endotoxin and of staphylococcal enterotoxin. J Bacteriol 87:1019–1026PubMedGoogle Scholar
  147. 147.
    Bachert C, Gevaert P, van Cauwenberge P (2002) Staphylococcus aureus enterotoxins: a key in airway disease? Allergy 57:480–487PubMedGoogle Scholar
  148. 148.
    Mariano NS, de Mello GC, Ferreira T, Schenka A, Camargo EA, de Nucci G et al (2010) Pre-exposure to staphylococcal enterotoxin A exacerbates the pulmonary allergic eosinophil recruitment in rats. Int Immunopharmacol 10:43–49PubMedGoogle Scholar
  149. 149.
    Bachert C, Gevaert P, Howarth P, Holtappels G, van Cauwenberge P, Johansson SG (2003) IgE to Staphylococcus aureus enterotoxins in serum is related to severity of asthma. J Allergy Clin Immunol 111:1131–1132PubMedGoogle Scholar
  150. 150.
    Rossi RE, Monasterolo G (2004) Prevalence of serum IgE antibodies to the Staphylococcus aureus enterotoxins (SAE, SEB, SEC, SED, TSST-1) in patients with persistent allergic rhinitis. Int Arch Allergy Immunol 133:261–266PubMedGoogle Scholar
  151. 151.
    O’Brien GJ, Riddell G, Elborn JS, Ennis M, Skibinski G (2006) Staphylococcus aureus enterotoxins induce IL-8 secretion by human nasal epithelial cells. Respir Res 7:115PubMedGoogle Scholar
  152. 152.
    Patou J, Gevaert P, Van Zele T, Holtappels G, van Cauwenberge P, Bachert C (2008) Staphylococcus aureus enterotoxin B, protein A, and lipoteichoic acid stimulations in nasal polyps. J Allergy Clin Immunol 121:110–115PubMedGoogle Scholar
  153. 153.
    Herz U, Ruckert R, Wollenhaupt K, Tschernig T, Neuhaus-Steinmetz U, Pabst R et al (1999) Airway exposure to bacterial superantigen (SEB) induces lymphocyte-dependent airway inflammation associated with increased airway responsiveness—a model for non-allergic asthma. Eur J Immunol 29:1021–1031PubMedGoogle Scholar
  154. 154.
    Desouza IA, Franco-Penteado CF, Camargo EA, Lima CS, Teixeira SA, Muscara MN et al (2006) Acute pulmonary inflammation induced by exposure of the airways to staphylococcal enterotoxin type B in rats. Toxicol Appl Pharmacol 217:107–113PubMedGoogle Scholar
  155. 155.
    Rajagopalan G, Iijima K, Singh M, Kita H, Patel R, David CS (2006) Intranasal exposure to bacterial superantigens induces airway inflammation in HLA class II transgenic mice. Infect Immun 74:1284–1296PubMedGoogle Scholar
  156. 156.
    Shinbori T, Matsuki M, Suga M, Kakimoto K, Ando M (1996) Induction of interstitial pneumonia in autoimmune mice by intratracheal administration of superantigen staphylococcal enterotoxin B. Cell Immunol 174:129–137PubMedGoogle Scholar
  157. 157.
    Hellings PW, Hens G, Meyts I, Bullens D, Vanoirbeek J, Gevaert P et al (2006) Aggravation of bronchial eosinophilia in mice by nasal and bronchial exposure to Staphylococcus aureus enterotoxin B. Clin Exp Allergy 36:1063–1071PubMedGoogle Scholar
  158. 158.
    Yu RL, Dong Z (2009) Proinflammatory impact of Staphylococcus aureus enterotoxin B on human nasal epithelial cells and inhibition by dexamethasone. Am J Rhinol Allergy 23:15–20PubMedGoogle Scholar
  159. 159.
    Nguyen T, Ghebrehiwet B, Peerschke EI (2000) Staphylococcus aureus protein A recognizes platelet gC1qR/p33: a novel mechanism for staphylococcal interactions with platelets. Infect Immun 68:2061–2068PubMedGoogle Scholar
  160. 160.
    Atkins KL, Burman JD, Chamberlain ES, Cooper JE, Poutrel B, Bagby S et al (2008) S. aureus IgG-binding proteins SpA and Sbi: host specificity and mechanisms of immune complex formation. Mol Immunol 45:1600–1611PubMedGoogle Scholar
  161. 161.
    Burman JD, Leung E, Atkins KL, O’Seaghdha MN, Lango L, Bernado P et al (2008) Interaction of human complement with Sbi, a staphylococcal immunoglobulin-binding protein: indications of a novel mechanism of complement evasion by Staphylococcus aureus. J Biol Chem 283:17579–17593PubMedGoogle Scholar
  162. 162.
    Rooijakkers SH, van Wamel WJ, Ruyken M, van Kessel KP, van Strijp JA (2005) Anti-opsonic properties of staphylokinase. Microbes Infect 7:476–484PubMedGoogle Scholar
  163. 163.
    Jin T, Bokarewa M, Foster T, Mitchell J, Higgins J, Tarkowski A (2004) Staphylococcus aureus resists human defensins by production of staphylokinase, a novel bacterial evasion mechanism. J Immunol 172:1169–1176PubMedGoogle Scholar
  164. 164.
    Verkaik NJ, Benard M, Boelens HA, de Vogel CP, Nouwen JL, Verbrugh HA et al (2011) Immune evasion cluster-positive bacteriophages are highly prevalent among human Staphylococcus aureus strains, but they are not essential in the first stages of nasal colonization. Clin Microbiol Infect 17:343–348PubMedGoogle Scholar
  165. 165.
    Rooijakkers SH, Ruyken M, Roos A, Daha MR, Presanis JS, Sim RB et al (2005) Immune evasion by a staphylococcal complement inhibitor that acts on C3 convertases. Nat Immunol 6:920–927PubMedGoogle Scholar
  166. 166.
    Postma B, Poppelier MJ, van Galen JC, Prossnitz ER, van Strijp JA, de Haas CJ et al (2004) Chemotaxis inhibitory protein of Staphylococcus aureus binds specifically to the C5a and formylated peptide receptor. J Immunol 172:6994–7001PubMedGoogle Scholar
  167. 167.
    de Haas CJ, Veldkamp KE, Peschel A, Weerkamp F, Van Wamel WJ, Heezius EC et al (2004) Chemotaxis inhibitory protein of Staphylococcus aureus, a bacterial antiinflammatory agent. J Exp Med 199:687–695PubMedGoogle Scholar
  168. 168.
    Jongerius I, Kohl J, Pandey MK, Ruyken M, van Kessel KP, van Strijp JA et al (2007) Staphylococcal complement evasion by various convertase-blocking molecules. J Exp Med 204:2461–2471PubMedGoogle Scholar
  169. 169.
    Movitz J (1976) Formation of extracellular protein A by Staphylococcus aureus. Eur J Biochem 68:291–299PubMedGoogle Scholar
  170. 170.
    Schneewind O, Model P, Fischetti VA (1992) Sorting of protein A to the staphylococcal cell wall. Cell 70:267–281PubMedGoogle Scholar
  171. 171.
    Shopsin B, Gomez M, Montgomery SO, Smith DH, Waddington M, Dodge DE et al (1999) Evaluation of protein A gene polymorphic region DNA sequencing for typing of Staphylococcus aureus strains. J Clin Microbiol 37:3556–3563PubMedGoogle Scholar
  172. 172.
    Koreen L, Ramaswamy SV, Graviss EA, Naidich S, Musser JM, Kreiswirth BN (2004) spa typing method for discriminating among Staphylococcus aureus isolates: implications for use of a single marker to detect genetic micro- and macrovariation. J Clin Microbiol 42:792–799PubMedGoogle Scholar
  173. 173.
    Martin FJ, Gomez MI, Wetzel DM, Memmi G, O’Seaghdha M, Soong G et al (2009) Staphylococcus aureus activates type I IFN signaling in mice and humans through the Xr repeated sequences of protein A. J Clin Invest 119:1931–1939PubMedGoogle Scholar
  174. 174.
    Kahl BC, Mellmann A, Deiwick S, Peters G, Harmsen D (2005) Variation of the polymorphic region X of the protein A gene during persistent airway infection of cystic fibrosis patients reflects two independent mechanisms of genetic change in Staphylococcus aureus. J Clin Microbiol 43:502–505PubMedGoogle Scholar
  175. 175.
    Hakoda M, Hayashimoto S, Yamanaka H, Terai C, Kamatani N, Kashiwazaki S (1994) Molecular basis for the interaction between human IgM and staphylococcal protein A. Clin Immunol Immunopathol 72:394–401PubMedGoogle Scholar
  176. 176.
    Kim HK, Cheng AG, Kim HY, Missiakas DM, Schneewind O (2010) Nontoxigenic protein A vaccine for methicillin-resistant Staphylococcus aureus infections in mice. J Exp Med 207:1863–1870PubMedGoogle Scholar
  177. 177.
    Gomez MI, Lee A, Reddy B, Muir A, Soong G, Pitt A et al (2004) Staphylococcus aureus protein A induces airway epithelial inflammatory responses by activating TNFR1. Nat Med 10:842–848PubMedGoogle Scholar
  178. 178.
    Palmqvist N, Foster T, Tarkowski A, Josefsson E (2002) Protein A is a virulence factor in Staphylococcus aureus arthritis and septic death. Microb Pathog 33:239–249PubMedGoogle Scholar
  179. 179.
    MacEwan DJ (2002) TNF receptor subtype signalling: differences and cellular consequences. Cell Signal 14:477–492PubMedGoogle Scholar
  180. 180.
    Gomez MI, Seaghdha MO, Prince AS (2007) Staphylococcus aureus protein A activates TACE through EGFR-dependent signaling. EMBO J 26:701–709PubMedGoogle Scholar
  181. 181.
    Gomez MI, O’Seaghdha M, Magargee M, Foster TJ, Prince AS (2006) Staphylococcus aureus protein A activates TNFR1 signaling through conserved IgG binding domains. J Biol Chem 281:20190–20196PubMedGoogle Scholar
  182. 182.
    Skerrett SJ, Liggitt HD, Hajjar AM, Wilson CB (2004) Cutting edge: myeloid differentiation factor 88 is essential for pulmonary host defense against Pseudomonas aeruginosa but not Staphylococcus aureus. J Immunol 172:3377–3381PubMedGoogle Scholar
  183. 183.
    Shaykhiev R, Behr J, Bals R (2008) Microbial patterns signaling via Toll-like receptors 2 and 5 contribute to epithelial repair, growth and survival. PLoS One 3:e1393PubMedGoogle Scholar
  184. 184.
    Basbaum C, Li D, Gensch E, Gallup M, Lemjabbar H (2002) Mechanisms by which Gram-positive bacteria and tobacco smoke stimulate mucin induction through the epidermal growth factor receptor (EGFR). Novartis Found Symp 248:171–176, discussion 176–180, 277–182PubMedGoogle Scholar
  185. 185.
    Miller LS, Cho JS (2011) Immunity against Staphylococcus aureus cutaneous infections. Nat Rev Immunol 11:505–518PubMedGoogle Scholar
  186. 186.
    Muir A, Soong G, Sokol S, Reddy B, Gomez MI, Van Heeckeren A et al (2004) Toll-like receptors in normal and cystic fibrosis airway epithelial cells. Am J Respir Cell Mol Biol 30:777–783PubMedGoogle Scholar
  187. 187.
    Mayer AK, Muehmer M, Mages J, Gueinzius K, Hess C, Heeg K et al (2007) Differential recognition of TLR-dependent microbial ligands in human bronchial epithelial cells. J Immunol 178:3134–3142PubMedGoogle Scholar
  188. 188.
    Greene CM, Carroll TP, Smith SG, Taggart CC, Devaney J, Griffin S et al (2005) TLR-induced inflammation in cystic fibrosis and non-cystic fibrosis airway epithelial cells. J Immunol 174:1638–1646PubMedGoogle Scholar
  189. 189.
    Sha Q, Truong-Tran AQ, Plitt JR, Beck LA, Schleimer RP (2004) Activation of airway epithelial cells by Toll-like receptor agonists. Am J Respir Cell Mol Biol 31:358–364PubMedGoogle Scholar
  190. 190.
    Xing Z, Harper R, Anunciacion J, Yang Z, Gao W, Qu B et al (2011) Host immune and apoptotic responses to avian influenza virus H9N2 in human tracheobronchial epithelial cells. Am J Respir Cell Mol Biol 44:24–33PubMedGoogle Scholar
  191. 191.
    von Aulock S, Morath S, Hareng L, Knapp S, van Kessel KP, van Strijp JA et al (2003) Lipoteichoic acid from Staphylococcus aureus is a potent stimulus for neutrophil recruitment. Immunobiology 208:413–422Google Scholar
  192. 192.
    Hoogerwerf JJ, de Vos AF, Bresser P, van der Zee JS, Pater JM, de Boer A et al (2008) Lung inflammation induced by lipoteichoic acid or lipopolysaccharide in humans. Am J Respir Crit Care Med 178:34–41PubMedGoogle Scholar
  193. 193.
    Quinn GA, Cole AM (2007) Suppression of innate immunity by a nasal carriage strain of Staphylococcus aureus increases its colonization on nasal epithelium. Immunology 122:80–89PubMedGoogle Scholar
  194. 194.
    Takeuchi O, Hoshino K, Akira S (2000) Cutting edge: TLR2-deficient and MyD88-deficient mice are highly susceptible to Staphylococcus aureus infection. J Immunol 165:5392–5396PubMedGoogle Scholar
  195. 195.
    Mullaly SC, Kubes P (2006) The role of TLR2 in vivo following challenge with Staphylococcus aureus and prototypic ligands. J Immunol 177:8154–8163PubMedGoogle Scholar
  196. 196.
    Bubeck Wardenburg J, Williams WA, Missiakas D (2006) Host defenses against Staphylococcus aureus infection require recognition of bacterial lipoproteins. Proc Natl Acad Sci USA 103:13831–13836PubMedGoogle Scholar
  197. 197.
    Saba S, Soong G, Greenberg S, Prince A (2002) Bacterial stimulation of epithelial G-CSF and GM-CSF expression promotes PMN survival in CF airways. Am J Respir Cell Mol Biol 27:561–567PubMedGoogle Scholar
  198. 198.
    Sorrentino R, de Souza PM, Sriskandan S, Duffin C, Paul-Clark MJ, Mitchell JA (2008) Pattern recognition receptors and interleukin-8 mediate effects of Gram-positive and Gram-negative bacteria on lung epithelial cell function. Br J Pharmacol 154:864–871PubMedGoogle Scholar
  199. 199.
    Ratner AJ, Bryan R, Weber A, Nguyen S, Barnes D, Pitt A et al (2001) Cystic fibrosis pathogens activate Ca2+-dependent mitogen-activated protein kinase signaling pathways in airway epithelial cells. J Biol Chem 276:19267–19275PubMedGoogle Scholar
  200. 200.
    Muller U, Steinhoff U, Reis LF, Hemmi S, Pavlovic J, Zinkernagel RM et al (1994) Functional role of type I and type II interferons in antiviral defense. Science 264:1918–1921PubMedGoogle Scholar
  201. 201.
    Der SD, Zhou A, Williams BR, Silverman RH (1998) Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays. Proc Natl Acad Sci USA 95:15623–15628PubMedGoogle Scholar
  202. 202.
    Parker D, Martin FJ, Soong G, Harfenist BS, Aguilar JL, Ratner AJ et al (2011) Streptococcus pneumoniae DNA initiates type I interferon signaling in the respiratory tract. MBio 2:e00016–11PubMedGoogle Scholar
  203. 203.
    Parker D, Cohen TS, Alhede M, Harfenist BS, Martin FJ, Prince A (2011) Induction of type I interferon signaling by Pseudomonas aeruginosa is diminished in cystic fibrosis epithelial cells. Am J Respir Cell Mol Biol Jul 21. [Epub ahead of print]Google Scholar
  204. 204.
    Decker T, Muller M, Stockinger S (2005) The yin and yang of type I interferon activity in bacterial infection. Nat Rev Immunol 5:675–687PubMedGoogle Scholar
  205. 205.
    Charrel-Dennis M, Latz E, Halmen KA, Trieu-Cuot P, Fitzgerald KA, Kasper DL et al (2008) TLR-independent type I interferon induction in response to an extracellular bacterial pathogen via intracellular recognition of its DNA. Cell Host Microbe 4:543–554PubMedGoogle Scholar
  206. 206.
    Toshchakov V, Jones BW, Perera PY, Thomas K, Cody MJ, Zhang S et al (2002) TLR4, but not TLR2, mediates IFN-beta-induced STAT1alpha/beta-dependent gene expression in macrophages. Nat Immunol 3:392–398PubMedGoogle Scholar
  207. 207.
    Mancuso G, Gambuzza M, Midiri A, Biondo C, Papasergi S, Akira S et al (2009) Bacterial recognition by TLR7 in the lysosomes of conventional dendritic cells. Nat Immunol 10:587–594PubMedGoogle Scholar
  208. 208.
    Chiu YH, Macmillan JB, Chen ZJ (2009) RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway. Cell 138:576–591PubMedGoogle Scholar
  209. 209.
    Sato M, Suemori H, Hata N, Asagiri M, Ogasawara K, Nakao K et al (2000) Distinct and essential roles of transcription factors IRF-3 and IRF-7 in response to viruses for IFN-alpha/beta gene induction. Immunity 13:539–548PubMedGoogle Scholar
  210. 210.
    Honda K, Yanai H, Negishi H, Asagiri M, Sato M, Mizutani T et al (2005) IRF-7 is the master regulator of type-I interferon-dependent immune responses. Nature 434:772–777PubMedGoogle Scholar
  211. 211.
    Schoenemeyer A, Barnes BJ, Mancl ME, Latz E, Goutagny N, Pitha PM et al (2005) The interferon regulatory factor, IRF5, is a central mediator of Toll-like receptor 7 signaling. J Biol Chem 280:17005–17012PubMedGoogle Scholar
  212. 212.
    Fitzgerald KA, McWhirter SM, Faia KL, Rowe DC, Latz E, Golenbock DT et al (2003) IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat Immunol 4:491–496PubMedGoogle Scholar
  213. 213.
    Schindler C, Plumlee C (2008) Inteferons pen the JAK-STAT pathway. Semin Cell Dev Biol 19:311–318PubMedGoogle Scholar
  214. 214.
    David M, Petricoin E 3rd, Benjamin C, Pine R, Weber MJ, Larner AC (1995) Requirement for MAP kinase (ERK2) activity in interferon alpha- and interferon beta-stimulated gene expression through STAT proteins. Science 269:1721–1723PubMedGoogle Scholar
  215. 215.
    Lenardo MJ, Fan CM, Maniatis T, Baltimore D (1989) The involvement of NF-kappa B in beta-interferon gene regulation reveals its role as widely inducible mediator of signal transduction. Cell 57:287–294PubMedGoogle Scholar
  216. 216.
    Manicone AM, Burkhart KM, Lu B, Clark JG (2008) CXCR3 ligands contribute to Th1-induced inflammation but not to homing of Th1 cells into the lung. Exp Lung Res 34:391–407PubMedGoogle Scholar
  217. 217.
    Qian C, An H, Yu Y, Liu S, Cao X (2007) TLR agonists induce regulatory dendritic cells to recruit Th1 cells via preferential IP-10 secretion and inhibit Th1 proliferation. Blood 109:3308–3315PubMedGoogle Scholar
  218. 218.
    Debes GF, Dahl ME, Mahiny AJ, Bonhagen K, Campbell DJ, Siegmund K et al (2006) Chemotactic responses of IL-4-, IL-10-, and IFN-gamma-producing CD4+ T cells depend on tissue origin and microbial stimulus. J Immunol 176:557–566PubMedGoogle Scholar
  219. 219.
    Martin FJ, Parker D, Harfenist BS, Soong G, Prince A (2011) Participation of CD11c(+) leukocytes in methicillin-resistant Staphylococcus aureus clearance from the lung. Infect Immun 79:1898–1904PubMedGoogle Scholar
  220. 220.
    Lappalainen U, Whitsett JA, Wert SE, Tichelaar JW, Bry K (2005) Interleukin-1beta causes pulmonary inflammation, emphysema, and airway remodeling in the adult murine lung. Am J Respir Cell Mol Biol 32:311–318PubMedGoogle Scholar
  221. 221.
    Martinon F, Burns K, Tschopp J (2002) The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell 10:417–426PubMedGoogle Scholar
  222. 222.
    Mariathasan S, Newton K, Monack DM, Vucic D, French DM, Lee WP et al (2004) Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. Nature 430:213–218PubMedGoogle Scholar
  223. 223.
    Bergsbaken T, Fink SL, Cookson BT (2009) Pyroptosis: host cell death and inflammation. Nat Rev Microbiol 7:99–109PubMedGoogle Scholar
  224. 224.
    Mariathasan S, Weiss DS, Newton K, McBride J, O’Rourke K, Roose-Girma M et al (2006) Cryopyrin activates the inflammasome in response to toxins and ATP. Nature 440:228–232PubMedGoogle Scholar
  225. 225.
    Bhakdi S, Muhly M, Korom S, Hugo F (1989) Release of interleukin-1 beta associated with potent cytocidal action of staphylococcal alpha-toxin on human monocytes. Infect Immun 57:3512–3519PubMedGoogle Scholar
  226. 226.
    Shimada T, Park BG, Wolf AJ, Brikos C, Goodridge HS, Becker CA et al (2010) Staphylococcus aureus evades lysozyme-based peptidoglycan digestion that links phagocytosis, inflammasome activation, and IL-1beta secretion. Cell Host Microbe 7:38–49PubMedGoogle Scholar
  227. 227.
    Chien YW, Klugman KP, Morens DM (2009) Bacterial pathogens and death during the 1918 influenza pandemic. N Engl J Med 361:2582–2583PubMedGoogle Scholar
  228. 228.
    Morens DM, Taubenberger JK, Fauci AS (2008) Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness. J Infect Dis 198:962–970PubMedGoogle Scholar
  229. 229.
    Lee MH, Arrecubieta C, Martin FJ, Prince A, Borczuk AC, Lowy FD (2010) A postinfluenza model of Staphylococcus aureus pneumonia. J Infect Dis 201:508–515PubMedGoogle Scholar
  230. 230.
    Small CL, Shaler CR, McCormick S, Jeyanathan M, Damjanovic D, Brown EG et al (2010) Influenza infection leads to increased susceptibility to subsequent bacterial superinfection by impairing NK cell responses in the lung. J Immunol 184:2048–2056PubMedGoogle Scholar
  231. 231.
    Kudva A, Scheller EV, Robinson KM, Crowe CR, Choi SM, Slight SR et al (2011) Influenza A inhibits Th17-mediated host defense against bacterial pneumonia in mice. J Immunol 186:1666–1674PubMedGoogle Scholar
  232. 232.
    Minegishi Y, Saito M, Nagasawa M, Takada H, Hara T, Tsuchiya S et al (2009) Molecular explanation for the contradiction between systemic Th17 defect and localized bacterial infection in hyper-IgE syndrome. J Exp Med 206:1291–1301PubMedGoogle Scholar
  233. 233.
    Frodermann V, Chau TA, Sayedyahossein S, Toth JM, Heinrichs DE, Madrenas J (2011) A modulatory interleukin-10 response to staphylococcal peptidoglycan prevents Th1/Th17 adaptive immunity to Staphylococcus aureus. J Infect Dis 204:253–262PubMedGoogle Scholar
  234. 234.
    Niebuhr M, Gathmann M, Scharonow H, Mamerow D, Mommert S, Balaji H et al (2011) Staphylococcal alpha-toxin is a strong inducer of interleukin-17 in humans. Infect Immun 79:1615–1622PubMedGoogle Scholar
  235. 235.
    Ishigame H, Kakuta S, Nagai T, Kadoki M, Nambu A, Komiyama Y et al (2009) Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses. Immunity 30:108–119PubMedGoogle Scholar
  236. 236.
    Ma CS, Chew GY, Simpson N, Priyadarshi A, Wong M, Grimbacher B et al (2008) Deficiency of Th17 cells in hyper IgE syndrome due to mutations in STAT3. J Exp Med 205:1551–1557PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Department of PediatricsColumbia UniversityNew YorkUSA

Personalised recommendations