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Immunology of Yersinia pestis Infection

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Yersinia pestis: Retrospective and Perspective

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 918))

Abstract

As a pathogen of plague, Yersinia pestis caused three massive pandemics in history that killed hundreds of millions of people. Yersinia pestis is highly invasive, causing severe septicemia which, if untreated, is usually fatal to its host. To survive in the host and maintain a persistent infection, Yersinia pestis uses several stratagems to evade the innate and the adaptive immune responses. For example, infections with this organism are biphasic, involving an initial “noninflammatory” phase where bacterial replication occurs initially with little inflammation and following by extensive phagocyte influx, inflammatory cytokine production, and considerable tissue destruction, which is called “proinflammatory” phase. In contrast, the host also utilizes its immune system to eliminate the invading bacteria. Neutrophil and macrophage are the first defense against Yersinia pestis invading through phagocytosis and killing. Other innate immune cells also play different roles, such as dendritic cells which help to generate more T helper cells. After several days post infection, the adaptive immune response begins to provide organism-specific protection and has a long-lasting immunological memory. Thus, with the cooperation and collaboration of innate and acquired immunity, the bacterium may be eliminated from the host. The research of Yersinia pestis and host immune systems provides an important topic to understand pathogen-host interaction and consequently develop effective countermeasures.

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References

  1. Lukaszewski RA, Kenny DJ, Taylor R, Rees DG, Hartley MG, Oyston PC. Pathogenesis of Yersinia pestis infection in BALB/c mice: effects on host macrophages and neutrophils. Infect Immun. 2005;73(11):7142–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Fukuto HS, Bliska JB. Editorial: Yersinia pestis survives in neutrophils and sends a PS to macrophages: bon appetit! J Leukoc Biol. 2014;95(3):383–5.

    Article  PubMed  CAS  Google Scholar 

  3. Spinner JL, Winfree S, Starr T, Shannon JG, Nair V, Steele-Mortimer O, Hinnebusch BJ. Yersinia pestis survival and replication within human neutrophil phagosomes and uptake of infected neutrophils by macrophages. J Leukoc Biol. 2014;95(3):389–98.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Bubeck SS, Cantwell AM, Dube PH. Delayed inflammatory response to primary pneumonic plague occurs in both outbred and inbred mice. Infect Immun. 2007;75(2):697–705.

    Article  CAS  PubMed  Google Scholar 

  5. Lathem WW, Price PA, Miller VL, Goldman WE. A plasminogen-activating protease specifically controls the development of primary pneumonic plague. Science. 2007;315(5811):509–13.

    Article  CAS  PubMed  Google Scholar 

  6. Lathem WW, Crosby SD, Miller VL, Goldman WE. Progression of primary pneumonic plague: a mouse model of infection, pathology, and bacterial transcriptional activity. Proc Natl Acad Sci U S A. 2005;102(49):17786–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sauvonnet N, Lambermont I, van der Bruggen P, Cornelis GR. YopH prevents monocyte chemoattractant protein 1 expression in macrophages and T-cell proliferation through inactivation of the phosphatidylinositol 3-kinase pathway. Mol Microbiol. 2002;45(3):805–15.

    Article  CAS  PubMed  Google Scholar 

  8. Orth K, Palmer LE, Bao ZQ, Stewart S, Rudolph AE, Bliska JB, Dixon JE. Inhibition of the mitogen-activated protein kinase kinase superfamily by a Yersinia effector. Science. 1999;285(5435):1920–3.

    Article  CAS  PubMed  Google Scholar 

  9. Viboud GI, Mejia E, Bliska JB. Comparison of YopE and YopT activities in counteracting host signalling responses to Yersinia pseudotuberculosis infection. Cell Microbiol. 2006;8(9):1504–15.

    Article  CAS  PubMed  Google Scholar 

  10. Brodsky IE, Palm NW, Sadanand S, Ryndak MB, Sutterwala FS, Flavell RA, Bliska JB, Medzhitov R. A Yersinia effector protein promotes virulence by preventing inflammasome recognition of the type III secretion system. Cell Host Microbe. 2010;7(5):376–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. LaRock CN, Cookson BT. The Yersinia virulence effector YopM binds caspase-1 to arrest inflammasome assembly and processing. Cell Host Microbe. 2012;12(6):799–805.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Brubaker RR. Interleukin-10 and inhibition of innate immunity to Yersiniae: roles of Yops and LcrV (V antigen). Infect Immun. 2003;71(7):3673–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. McDonald C, Vacratsis PO, Bliska JB, Dixon JE. The yersinia virulence factor YopM forms a novel protein complex with two cellular kinases. J Biol Chem. 2003;278:18514–23.

    Article  CAS  PubMed  Google Scholar 

  14. Osei-Owusu P, Jessen Condry DL, Toosky M, Roughead W, Bradley DS, Nilles ML. The N terminus of type III secretion needle protein YscF from Yersinia pestis functions to modulate innate immune responses. Infect Immun. 2015;83(4):1507–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Rebeil R, Ernst RK, Jarrett CO, Adams KN, Miller SI, Hinnebusch BJ. Characterization of late acyltransferase genes of Yersinia pestis and their role in temperature-dependent lipid A variation. J Bacteriol. 2006;188(4):1381–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Tan L, Darby C. Yersinia pestis is viable with endotoxin composed of only lipid A. J Bacteriol. 2005;187(18):6599–600.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Montminy SW, Khan N, McGrath S, Walkowicz MJ, Sharp F, Conlon JE, Fukase K, Kusumoto S, Sweet C, Miyake K, et al. Virulence factors of Yersinia pestis are overcome by a strong lipopolysaccharide response. Nat Immunol. 2006;7(10):1066–73.

    Article  CAS  PubMed  Google Scholar 

  18. de la Puerta ML, Trinidad AG, del Carmen Rodriguez M, Bogetz J, Sanchez Crespo M, Mustelin T, Alonso A, Bayon Y. Characterization of new substrates targeted by Yersinia tyrosine phosphatase YopH. PLoS One. 2009;4(2):e4431.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Hamid N, Gustavsson A, Andersson K, McGee K, Persson C, Rudd CE, Fallman M. YopH dephosphorylates Cas and Fyn-binding protein in macrophages. Microb Pathog. 1999;27(4):231–42.

    Article  CAS  PubMed  Google Scholar 

  20. Persson C, Carballeira N, Wolf-Watz H, Fallman M. The PTPase YopH inhibits uptake of Yersinia, tyrosine phosphorylation of p130Cas and FAK, and the associated accumulation of these proteins in peripheral focal adhesions. EMBO J. 1997;16(9):2307–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Weidow CL, Black DS, Bliska JB, Bouton AH. CAS/Crk signalling mediates uptake of Yersinia into human epithelial cells. Cell Microbiol. 2000;2(6):549–60.

    Article  CAS  PubMed  Google Scholar 

  22. Von Pawel-Rammingen U, Telepnev MV, Schmidt G, Aktories K, Wolf-Watz H, Rosqvist R. GAP activity of the Yersinia YopE cytotoxin specifically targets the Rho pathway: a mechanism for disruption of actin microfilament structure. Mol Microbiol. 2000;36(3):737–48.

    Article  Google Scholar 

  23. Roppenser B, Roder A, Hentschke M, Ruckdeschel K, Aepfelbacher M. Yersinia enterocolitica differentially modulates RhoG activity in host cells. J Cell Sci. 2009;122(Pt 5):696–705.

    Article  CAS  PubMed  Google Scholar 

  24. Andor A, Trulzsch K, Essler M, Roggenkamp A, Wiedemann A, Heesemann J, Aepfelbacher M. YopE of Yersinia, a GAP for Rho GTPases, selectively modulates Rac-dependent actin structures in endothelial cells. Cell Microbiol. 2001;3(5):301–10.

    Article  CAS  PubMed  Google Scholar 

  25. Shao F, Dixon JE. YopT is a cysteine protease cleaving Rho family GTPases. Adv Exp Med Biol. 2003;529:79–84.

    Article  PubMed  Google Scholar 

  26. Rosqvist R, Forsberg A, Rimpilainen M, Bergman T, Wolf-Watz H. The cytotoxic protein YopE of Yersinia obstructs the primary host defence. Mol Microbiol. 1990;4(4):657–67.

    Article  CAS  PubMed  Google Scholar 

  27. Andersson K, Carballeira N, Magnusson KE, Persson C, Stendahl O, Wolf-Watz H, Fallman M. YopH of Yersinia pseudotuberculosis interrupts early phosphotyrosine signalling associated with phagocytosis. Mol Microbiol. 1996;20(5):1057–69.

    Article  CAS  PubMed  Google Scholar 

  28. Iriarte M, Cornelis GR. YopT, a new Yersinia Yop effector protein, affects the cytoskeleton of host cells. Mol Microbiol. 1998;29(3):915–29.

    Article  CAS  PubMed  Google Scholar 

  29. Aepfelbacher M, Heesemann J. Modulation of Rho GTPases and the actin cytoskeleton by Yersinia outer proteins (Yops). Int J Med Microbiol. 2001;291(4):269–76.

    Article  CAS  PubMed  Google Scholar 

  30. Aepfelbacher M, Zumbihl R, Heesemann J. Modulation of Rho GTPases and the actin cytoskeleton by YopT of Yersinia. Curr Top Microbiol Immunol. 2005;291:167–75.

    CAS  PubMed  Google Scholar 

  31. Du Y, Rosqvist R, Forsberg A. Role of fraction 1 antigen of Yersinia pestis in inhibition of phagocytosis. Infect Immun. 2002;70(3):1453–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Payne D, Tatham D, Williamson ED, Titball RW. The pH 6 antigen of Yersinia pestis binds to beta1-linked galactosyl residues in glycosphingolipids. Infect Immun. 1998;66(9):4545–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Makoveichuk E, Cherepanov P, Lundberg S, Forsberg A, Olivecrona G. pH6 antigen of Yersinia pestis interacts with plasma lipoproteins and cell membranes. J Lipid Res. 2003;44(2):320–30.

    Article  CAS  PubMed  Google Scholar 

  34. Anisimov AP, Dentovskaya SV, Titareva GM, Bakhteeva IV, Shaikhutdinova RZ, Balakhonov SV, Lindner B, Kocharova NA, Senchenkova SN, Holst O, et al. Intraspecies and temperature-dependent variations in susceptibility of Yersinia pestis to the bactericidal action of serum and to polymyxin B. Infect Immun. 2005;73(11):7324–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Bliska JB, Falkow S. Bacterial resistance to complement killing mediated by the Ail protein of Yersinia enterocolitica. Proc Natl Acad Sci U S A. 1992;89(8):3561–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Kirjavainen V, Jarva H, Biedzka-Sarek M, Blom AM, Skurnik M, Meri S. Yersinia enterocolitica serum resistance proteins YadA and ail bind the complement regulator C4b-binding protein. PLoS Pathog. 2008;4(8):e1000140.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Skorek K, Raczkowska A, Dudek B, Mietka K, Guz-Regner K, Pawlak A, Klausa E, Bugla-Ploskonska G, Brzostek K. Regulatory protein OmpR influences the serum resistance of Yersinia enterocolitica O:9 by modifying the structure of the outer membrane. PLoS One. 2013;8(11):e79525.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Porat R, McCabe WR, Brubaker RR. Lipopolysaccharide-associated resistance to killing of yersiniae by complement. J Endotoxin Res. 1995;2:91–7.

    CAS  Google Scholar 

  39. Kolodziejek AM, Sinclair DJ, Seo KS, Schnider DR, Deobald CF, Rohde HN, Viall AK, Minnich SS, Hovde CJ, Minnich SA, et al. Phenotypic characterization of OmpX, an Ail homologue of Yersinia pestis KIM. Microbiology. 2007;153(Pt 9):2941–51.

    Article  CAS  PubMed  Google Scholar 

  40. Bartra SS, Styer KL, O’Bryant DM, Nilles ML, Hinnebusch BJ, Aballay A, Plano GV. Resistance of Yersinia pestis to complement-dependent killing is mediated by the Ail outer membrane protein. Infect Immun. 2008;76(2):612–22.

    Article  CAS  PubMed  Google Scholar 

  41. Biedzka-Sarek M, Jarva H, Hyytiainen H, Meri S, Skurnik M. Characterization of complement factor H binding to Yersinia enterocolitica serotype O:3. Infect Immun. 2008;76(9):4100–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Biedzka-Sarek M, Salmenlinna S, Gruber M, Lupas AN, Meri S, Skurnik M. Functional mapping of YadA- and Ail-mediated binding of human factor H to Yersinia enterocolitica serotype O:3. Infect Immun. 2008;76(11):5016–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Ho DK, Riva R, Kirjavainen V, Jarva H, Ginstrom E, Blom AM, Skurnik M, Meri S. Functional recruitment of the human complement inhibitor C4BP to Yersinia pseudotuberculosis outer membrane protein Ail. J Immunol. 2012;188(9):4450–9.

    Article  CAS  PubMed  Google Scholar 

  44. Sebbane F, Jarrett CO, Gardner D, Long D, Hinnebusch BJ. Role of the Yersinia pestis plasminogen activator in the incidence of distinct septicemic and bubonic forms of flea-borne plague. Proc Natl Acad Sci U S A. 2006;103(14):5526–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Sodeinde OA, Subrahmanyam YV, Stark K, Quan T, Bao Y, Goguen JD. A surface protease and the invasive character of plague. Science. 1992;258(5084):1004–7.

    Article  CAS  PubMed  Google Scholar 

  46. Drozdov IG, Anisimov AP, Samoilova SV, Yezhov IN, Yeremin SA, Karlyshev AV, Krasilnikova VM, Kravchenko VI. Virulent non-capsulate Yersinia pestis variants constructed by insertion mutagenesis. J Med Microbiol. 1995;42(4):264–8.

    Article  CAS  PubMed  Google Scholar 

  47. Samoilova SV, Samoilova LV, Yezhov IN, Drozdov IG, Anisimov AP. Virulence of pPst + and pPst- strains of Yersinia pestis for guinea-pigs. J Med Microbiol. 1996;45(6):440–4.

    Article  CAS  PubMed  Google Scholar 

  48. Laudisoit A, Leirs H, Makundi RH, Van Dongen S, Davis S, Neerinckx S, Deckers J, Libois R. Plague and the human flea Tanzania. Emerg Infect Dis. 2007;13(5):687–93.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Zhang SS, Park CG, Zhang P, Bartra SS, Plano GV, Klena JD, Skurnik M, Hinnebusch BJ, Chen T. Plasminogen activator Pla of Yersinia pestis utilizes murine DEC-205 (CD205) as a receptor to promote dissemination. J Biol Chem. 2008;283(46):31511–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Reboul A, Lemaitre N, Titecat M, Merchez M, Deloison G, Ricard I, Pradel E, Marceau M, Sebbane F. Yersinia pestis requires the 2-component regulatory system OmpR-EnvZ to resist innate immunity during the early and late stages of plague. J Infect Dis. 2014;210(9):1367–75.

    Article  PubMed  Google Scholar 

  51. Marketon MM, DePaolo RW, DeBord KL, Jabri B, Schneewind O. Plague bacteria target immune cells during infection. Science. 2005;309(5741):1739–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Pechous RD, Sivaraman V, Price PA, Stasulli NM, Goldman WE. Early host cell targets of Yersinia pestis during primary pneumonic plague. PLoS Pathog. 2013;9(10):e1003679.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Busch JD, Van Andel R, Stone NE, Cobble KR, Nottingham R, Lee J, Versteeg M, Corcoran J, Cordova J, Van Pelt W, et al. The innate immune response may be important for surviving plague in wild gunnison’s prairie dogs. J Wildl Dis. 2013;49(4):920–31.

    Article  PubMed  Google Scholar 

  54. Cavanaugh DC, Randall R. The role of multiplication of Pasteurella pestis in mononuclear phagocytes in the pathogenesis of flea-borne plague. J Immunol. 1959;83:348–63.

    CAS  PubMed  Google Scholar 

  55. Elvin SJ, Williamson ED, Scott JC, Smith JN, De Lema Perez G, Chilla S, Clapham P, Pfeffer K, Schlondorff D, Luckow B. Evolutionary genetics: ambiguous role of CCR5 in Y. pestis infection. Nature. 2004;430(6998):417.

    Article  CAS  PubMed  Google Scholar 

  56. Pujol C, Bliska JB. The ability to replicate in macrophages is conserved between Yersinia pestis and Yersinia pseudotuberculosis. Infect Immun. 2003;71(10):5892–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Straley SC, Harmon PA. Yersinia pestis grows within phagolysosomes in mouse peritoneal macrophages. Infect Immun. 1984;45(3):655–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Pujol C, Bliska JB. Turning Yersinia pathogenesis outside in: subversion of macrophage function by intracellular yersiniae. Clin Immunol. 2005;114(3):216–26.

    Article  CAS  PubMed  Google Scholar 

  59. Zhou D, Han Y, Yang R. Molecular and physiological insights into plague transmission, virulence and etiology. Microbes Infect. 2006;8(1):273–84.

    Article  CAS  PubMed  Google Scholar 

  60. Weeks S, Hill J, Friedlander A, Welkos S. Anti-V antigen antibody protects macrophages from Yersinia pestis-induced cell death and promotes phagocytosis. Microb Pathog. 2002;32(5):227–37.

    Article  CAS  PubMed  Google Scholar 

  61. Bergsbaken T, Cookson BT. Macrophage activation redirects yersinia-infected host cell death from apoptosis to caspase-1-dependent pyroptosis. PLoS Pathog. 2007;3(11):e161.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Ruckdeschel K, Pfaffinger G, Haase R, Sing A, Weighardt H, Hacker G, Holzmann B, Heesemann J. Signaling of apoptosis through TLRs critically involves toll/IL-1 receptor domain-containing adapter inducing IFN-beta, but not MyD88, in bacteria-infected murine macrophages. J Immunol. 2004;173(5):3320–8.

    Article  CAS  PubMed  Google Scholar 

  63. Hoebe K, Du X, Georgel P, Janssen E, Tabeta K, Kim SO, Goode J, Lin P, Mann N, Mudd S, et al. Identification of Lps2 as a key transducer of MyD88-independent TIR signalling. Nature. 2003;424(6950):743–8.

    Article  CAS  PubMed  Google Scholar 

  64. Zhang Y, Ting AT, Marcu KB, Bliska JB. Inhibition of MAPK and NF-kappa B pathways is necessary for rapid apoptosis in macrophages infected with Yersinia. J Immunol. 2005;174(12):7939–49.

    Article  CAS  PubMed  Google Scholar 

  65. Karin M, Lin A. NF-kappaB at the crossroads of life and death. Nat Immunol. 2002;3(3):221–7.

    Article  CAS  PubMed  Google Scholar 

  66. Palmer LE, Hobbie S, Galan JE, Bliska JB. YopJ of Yersinia pseudotuberculosis is required for the inhibition of macrophage TNF-alpha production and downregulation of the MAP kinases p38 and JNK. Mol Microbiol. 1998;27(5):953–65.

    Article  CAS  PubMed  Google Scholar 

  67. Schesser K, Spiik AK, Dukuzumuremyi JM, Neurath MF, Pettersson S, Wolf-Watz H. The yopJ locus is required for Yersinia-mediated inhibition of NF-kappaB activation and cytokine expression: yopJ contains a eukaryotic SH2-like domain that is essential for its repressive activity. Mol Microbiol. 1998;28(6):1067–79.

    Article  CAS  PubMed  Google Scholar 

  68. Denecker G, Declercq W, Geuijen CA, Boland A, Benabdillah R, van Gurp M, Sory MP, Vandenabeele P, Cornelis GR. Yersinia enterocolitica YopP-induced apoptosis of macrophages involves the apoptotic signaling cascade upstream of bid. J Biol Chem. 2001;276(23):19706–14.

    Article  CAS  PubMed  Google Scholar 

  69. Savill J, Dransfield I, Gregory C, Haslett C. A blast from the past: clearance of apoptotic cells regulates immune responses. Nat Rev Immunol. 2002;2(12):965–75.

    Article  CAS  PubMed  Google Scholar 

  70. Voll RE, Herrmann M, Roth EA, Stach C, Kalden JR, Girkontaite I. Immunosuppressive effects of apoptotic cells. Nature. 1997;390(6658):350–1.

    Article  CAS  PubMed  Google Scholar 

  71. Fantuzzi G, Dinarello CA. Interleukin-18 and interleukin-1 beta: two cytokine substrates for ICE (caspase-1). J Clin Immunol. 1999;19(1):1–11.

    Article  CAS  PubMed  Google Scholar 

  72. Sebbane F, Gardner D, Long D, Gowen BB, Hinnebusch BJ. Kinetics of disease progression and host response in a rat model of bubonic plague. Am J Pathol. 2005;166(5):1427–39.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Balada-Llasat JM, Mecsas J. Yersinia has a tropism for B and T cell zones of lymph nodes that is independent of the type III secretion system. PLoS Pathog. 2006;2(9), e86.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Guinet F, Ave P, Jones L, Huerre M, Carniel E. Defective innate cell response and lymph node infiltration specify Yersinia pestis infection. PLoS One. 2008;3(2):e1688.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Mills SD, Boland A, Sory MP, van der Smissen P, Kerbourch C, Finlay BB, Cornelis GR. Yersinia enterocolitica induces apoptosis in macrophages by a process requiring functional type III secretion and translocation mechanisms and involving YopP, presumably acting as an effector protein. Proc Natl Acad Sci U S A. 1997;94(23):12638–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Monack DM, Mecsas J, Ghori N, Falkow S. Yersinia signals macrophages to undergo apoptosis and YopJ is necessary for this cell death. Proc Natl Acad Sci U S A. 1997;94(19):10385–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Ruckdeschel K, Roggenkamp A, Lafont V, Mangeat P, Heesemann J, Rouot B. Interaction of Yersinia enterocolitica with macrophages leads to macrophage cell death through apoptosis. Infect Immun. 1997;65(11):4813–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Shin H, Cornelis GR. Type III secretion translocation pores of Yersinia enterocolitica trigger maturation and release of pro-inflammatory IL-1beta. Cell Microbiol. 2007;9(12):2893–902.

    Article  CAS  PubMed  Google Scholar 

  79. Laws TR, Davey MS, Titball RW, Lukaszewski R. Neutrophils are important in early control of lung infection by Yersinia pestis. Microbes Infect. 2010;12(4):331–5.

    Article  CAS  PubMed  Google Scholar 

  80. Shannon JG, Bosio CF, Hinnebusch BJ. Dermal neutrophil, macrophage and dendritic cell responses to Yersinia pestis transmitted by fleas. PLoS Pathog. 2015;11(3), e1004734.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Vagima Y, Zauberman A, Levy Y, Gur D, Tidhar A, Aftalion M, Shafferman A, Mamroud E. Circumventing Y. pestis Virulence by Early Recruitment of Neutrophils to the Lungs during Pneumonic Plague. PLoS Pathog. 2015;11(5):e1004893.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Bi Y, Zhou J, Yang H, Wang X, Zhang X, Wang Q, Wu X, Han Y, Song Y, Tan Y, et al. IL-17A produced by neutrophils protects against pneumonic plague through orchestrating IFN-gamma-activated macrophage programming. J Immunol. 2014;192(2):704–13.

    Article  CAS  PubMed  Google Scholar 

  83. Merritt PM, Nero T, Bohman L, Felek S, Krukonis ES, Marketon MM. Yersinia pestis targets neutrophils via complement receptor 3. Cell Microbiol. 2015;17(5):666–87.

    Article  CAS  PubMed  Google Scholar 

  84. Hinnebusch BJ, Jarrett CO, Callison JA, Gardner D, Buchanan SK, Plano GV. Role of the Yersinia pestis Ail protein in preventing a protective polymorphonuclear leukocyte response during bubonic plague. Infect Immun. 2011;79(12):4984–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Velan B, Bar-Haim E, Zauberman A, Mamroud E, Shafferman A, Cohen S. Discordance in the effects of Yersinia pestis on the dendritic cell functions manifested by induction of maturation and paralysis of migration. Infect Immun. 2006;74(11):6365–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Robinson RT, Khader SA, Locksley RM, Lien E, Smiley ST, Cooper AM. Yersinia pestis evades TLR4-dependent induction of IL-12(p40)2 by dendritic cells and subsequent cell migration. J Immunol. 2008;181(8):5560–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Depaolo RW, Tang F, Kim I, Han M, Levin N, Ciletti N, Lin A, Anderson D, Schneewind O, Jabri B. Toll-like receptor 6 drives differentiation of tolerogenic dendritic cells and contributes to LcrV-mediated plague pathogenesis. Cell Host Microbe. 2008;4(4):350–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Kingston R, Burke F, Robinson JH, Bedford PA, Jones SM, Knight SC, Williamson ED. The fraction 1 and V protein antigens of Yersinia pestis activate dendritic cells to induce primary T cell responses. Clin Exp Immunol. 2007;149(3):561–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Do Y, Koh H, Park CG, Dudziak D, Seo P, Mehandru S, Choi JH, Cheong C, Park S, Perlin DS, et al. Targeting of LcrV virulence protein from Yersinia pestis to dendritic cells protects mice against pneumonic plague. Eur J Immunol. 2010;40(10):2791–6.

    Article  CAS  PubMed  Google Scholar 

  90. Kerschen EJ, Cohen DA, Kaplan AM, Straley SC. The plague virulence protein YopM targets the innate immune response by causing a global depletion of NK cells. Infect Immun. 2004;72(8):4589–602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Ye Z, Kerschen EJ, Cohen DA, Kaplan AM, van Rooijen N, Straley SC. Gr1+ cells control growth of YopM-negative Yersinia pestis during systemic plague. Infect Immun. 2009;77(9):3791–806.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Green M, Rogers D, Russell P, Stagg AJ, Bell DL, Eley SM, Titball RW, Williamson ED. The SCID/Beige mouse as a model to investigate protection against Yersinia pestis. FEMS Immunol Med Microbiol. 1999;23(2):107–13.

    Article  CAS  PubMed  Google Scholar 

  93. Parent MA, Berggren KN, Kummer LW, Wilhelm LB, Szaba FM, Mullarky IK, Smiley ST. Cell-mediated protection against pulmonary Yersinia pestis infection. Infect Immun. 2005;73(11):7304–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Lin JS, Park S, Adamovicz JJ, Hill J, Bliska JB, Cote CK, Perlin DS, Amemiya K, Smiley ST. TNFalpha and IFNgamma contribute to F1/LcrV-targeted immune defense in mouse models of fully virulent pneumonic plague. Vaccine. 2010;29(2):357–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Levy Y, Flashner Y, Tidhar A, Zauberman A, Aftalion M, Lazar S, Gur D, Shafferman A, Mamroud E. T cells play an essential role in anti-F1 mediated rapid protection against bubonic plague. Vaccine. 2011;29(40):6866–73.

    Article  CAS  PubMed  Google Scholar 

  96. Li B, Zhou L, Guo J, Wang X, Ni B, Ke Y, Zhu Z, Guo Z, Yang R. High-throughput identification of new protective antigens from a Yersinia pestis live vaccine by enzyme-linked immunospot assay. Infect Immun. 2009;77(10):4356–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Bi Y, Liu G, Yang R. Reciprocal modulation between TH17 and other helper T cell lineages. J Cell Physiol. 2011;226(1):8–13.

    Article  CAS  PubMed  Google Scholar 

  98. Elvin SJ, Williamson ED. Stat 4 but not Stat 6 mediated immune mechanisms are essential in protection against plague. Microb Pathog. 2004;37(4):177–84.

    Article  CAS  PubMed  Google Scholar 

  99. Dinc G, Pennington JM, Yolcu ES, Lawrenz MB, Shirwan H. Improving the Th1 cellular efficacy of the lead Yersinia pestis rF1-V subunit vaccine using SA-4-1BBL as a novel adjuvant. Vaccine. 2014;32(39):5035–40.

    Article  CAS  PubMed  Google Scholar 

  100. Lin JS, Kummer LW, Szaba FM, Smiley ST. IL-17 contributes to cell-mediated defense against pulmonary Yersinia pestis infection. J Immunol. 2011;186(3):1675–84.

    Article  CAS  PubMed  Google Scholar 

  101. Lin JS, Szaba FM, Kummer LW, Chromy BA, Smiley ST. Yersinia pestis YopE contains a dominant CD8 T cell epitope that confers protection in a mouse model of pneumonic plague. J Immunol. 2011;187(2):897–904.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Szaba FM, Kummer LW, Duso DK, Koroleva EP, Tumanov AV, Cooper AM, Bliska JB, Smiley ST, Lin JS. TNFalpha and IFNgamma but not perforin are critical for CD8 T cell-mediated protection against pulmonary Yersinia pestis infection. PLoS Pathog. 2014;10(5):e1004142.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. Philipovskiy AV, Smiley ST. Vaccination with live Yersinia pestis primes CD4 and CD8 T cells that synergistically protect against lethal pulmonary Y. pestis infection. Infect Immun. 2007;75(2):878–85.

    Article  CAS  PubMed  Google Scholar 

  104. Anderson Jr GW, Leary SE, Williamson ED, Titball RW, Welkos SL, Worsham PL, Friedlander AM. Recombinant V antigen protects mice against pneumonic and bubonic plague caused by F1-capsule-positive and -negative strains of Yersinia pestis. Infect Immun. 1996;64(11):4580–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Andrews GP, Heath DG, Anderson Jr GW, Welkos SL, Friedlander AM. Fraction 1 capsular antigen (F1) purification from Yersinia pestis CO92 and from an Escherichia coli recombinant strain and efficacy against lethal plague challenge. Infect Immun. 1996;64(6):2180–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. DeBord KL, Anderson DM, Marketon MM, Overheim KA, DePaolo RW, Ciletti NA, Jabri B, Schneewind O. Immunogenicity and protective immunity against bubonic plague and pneumonic plague by immunization of mice with the recombinant V10 antigen, a variant of LcrV. Infect Immun. 2006;74(8):4910–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Leary SE, Griffin KF, Garmory HS, Williamson ED, Titball RW. Expression of an F1/V fusion protein in attenuated Salmonella typhimurium and protection of mice against plague. Microb Pathog. 1997;23(3):167–79.

    Article  CAS  PubMed  Google Scholar 

  108. Li B, Zhou D, Wang Z, Song Z, Wang H, Li M, Dong X, Wu M, Guo Z, Yang R. Antibody profiling in plague patients by protein microarray. Microbes Infect. 2008;10(1):45–51.

    Article  PubMed  CAS  Google Scholar 

  109. Rasoamanana B, Leroy F, Boisier P, Rasolomaharo M, Buchy P, Carniel E, Chanteau S. Field evaluation of an immunoglobulin G anti-F1 enzyme-linked immunosorbent assay for serodiagnosis of human plague in Madagascar. Clin Diagn Lab Immunol. 1997;4(5):587–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Li B, Du C, Zhou L, Bi Y, Wang X, Wen L, Guo Z, Song Z, Yang R. Humoral and cellular immune responses to Yersinia pestis infection in long-term recovered plague patients. Clin Vaccine Immunol. 2012;19(2):228–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Qi Z, Zhao H, Zhang Q, Bi Y, Ren L, Zhang X, Yang H, Yang X, Wang Q, Li C, et al. Acquisition of maternal antibodies both from the placenta and by lactation protects mouse offspring from Yersinia pestis challenge. Clin Vaccine Immunol. 2012;19(11):1746–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Zhang X, Wang Q, Bi Y, Kou Z, Zhou J, Cui Y, Yan Y, Zhou L, Tan Y, Yang H, et al. Kinetics of memory B cell and plasma cell responses in the mice immunized with plague vaccines. Scand J Immunol. 2014;79(3):157–62.

    Article  CAS  PubMed  Google Scholar 

  113. Shenoy GN, Chatterjee P, Kaw S, Mukherjee S, Rathore DK, Bal V, Rath S, George A. Recruitment of memory B cells to lymph nodes remote from the site of immunization requires an inflammatory stimulus. J Immunol. 2012;189(2):521–8.

    Article  CAS  PubMed  Google Scholar 

  114. Williamson ED, Flick-Smith HC, Waters E, Miller J, Hodgson I, Le Butt CS, Hill J. Immunogenicity of the rF1 + rV vaccine for plague with identification of potential immune correlates. Microb Pathog. 2007;42(1):11–21.

    Article  CAS  PubMed  Google Scholar 

  115. Bashaw J, Norris S, Weeks S, Trevino S, Adamovicz JJ, Welkos S. Development of in vitro correlate assays of immunity to infection with Yersinia pestis. Clin Vaccine Immunol. 2007;14(5):605–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Cowan C, Philipovskiy AV, Wulff-Strobel CR, Ye Z, Straley SC. Anti-LcrV antibody inhibits delivery of Yops by Yersinia pestis KIM5 by directly promoting phagocytosis. Infect Immun. 2005;73(9):6127–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Parent MA, Wilhelm LB, Kummer LW, Szaba FM, Mullarky IK, Smiley ST. Gamma interferon, tumor necrosis factor alpha, and nitric oxide synthase 2, key elements of cellular immunity, perform critical protective functions during humoral defense against lethal pulmonary Yersinia pestis infection. Infect Immun. 2006;74(6):3381–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Beijing Institute of Microbiology and Epidemiology, No. Dongdajie, Fengtai, Beijing, 100071, China

    Yujing Bi

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  1. Beijing Institute of Microbiology and Epidemiology, Beijing, China

    Ruifu Yang

  2. State Research Center for Applied Microbiology, Moscow Region, Russia

    Andrey Anisimov

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Bi, Y. (2016). Immunology of Yersinia pestis Infection. In: Yang, R., Anisimov, A. (eds) Yersinia pestis: Retrospective and Perspective. Advances in Experimental Medicine and Biology, vol 918. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-0890-4_10

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