The Microbial Endocrinology of Pseudomonas aeruginosa: Inflammatory and Immune Perspectives

  • Valerie F. L. Yong
  • Min Min Soh
  • Tavleen Kaur Jaggi
  • Micheál Mac Aogáin
  • Sanjay H. Chotirmall


Pseudomonas aeruginosa is a major pathogen responsible for both acute and chronic infection. Known as a colonising pathogen of the cystic fibrosis (CF) lung, it is implicated in other settings such as bronchiectasis. It has the ability to cause acute disseminated or localised infection particularly in the immunocompromised. Human hormones have been highlighted as potential regulators of bacterial virulence through crosstalk between analogous “quorum sensing” (QS) systems present in the bacteria that respond to mammalian hormones. Pseudomonas aeruginosa is known to utilise interconnected QS systems to coordinate its virulence and evade various aspects of the host immune system activated in response to infection. Several human hormones demonstrate an influence on P. aeruginosa growth and virulence. This inter-kingdom signalling, termed “microbial endocrinology” has important implications for host–microbe interaction during infection and, potentially opens up novel avenues for therapeutic intervention. This phenomenon, supported by the existence of sexual dichotomies in both microbial infection and chronic lung diseases such as CF is potentially explained by sex hormones and their influence on the infective process. This review summarises our current understanding of the microbial endocrinology of P. aeruginosa, including its endogenous QS systems and their intersection with human endocrinology, pathogenesis of infection and the host immune system.


Pseudomonas aeruginosa Endocrinology Sex hormones Immunology Quorum sensing 



This research is supported by a Lee Kong Chian School of Medicine, Nanyang Technological University Start-Up Grant (S.H.C).

Compliance with Ethical Standards

Conflict of interest

All authors have no conflicts of interest to disclose.


  1. Alcaniz L, Vega A, Chacón P et al (2013) Histamine production by human neutrophils. FASEB J 27:2902–2910PubMedCrossRefGoogle Scholar
  2. Anas AA, van Lieshout MH, Claushuis TA et al (2016) Lung epithelial MyD88 drives early pulmonary clearance of Pseudomonas aeruginosa by a flagellin dependent mechanism. Am J Physiol Lung Cell Mol Physiol 311:L219–L228PubMedGoogle Scholar
  3. Beury-Cirou A, Tannières M, Minard C et al (2013) At a supra-physiological concentration, human sexual hormones act as quorum-sensing inhibitors. PLoS One 8:e83564PubMedPubMedCentralCrossRefGoogle Scholar
  4. Blier AS, Veron W, Bazire A et al (2011) C-type natriuretic peptide modulates quorum sensing molecule and toxin production in Pseudomonas aeruginosa. Microbiology 157(Pt 7):1929–1944PubMedPubMedCentralCrossRefGoogle Scholar
  5. Brunelleschi S (2016) Immune response and auto-immune diseases: gender does matter and makes the difference. Italian J Gender Specific Med 2:5–14Google Scholar
  6. Chotirmall SH (2014) The microbiological gender gap in cystic fibrosis. J Womens Health 23:995–996CrossRefGoogle Scholar
  7. Chotirmall SH, Greene CM, Oglesby IK et al (2010) 17Beta-estradiol inhibits IL-8 in cystic fibrosis by up-regulating secretory leucoprotease inhibitor. Am J Respir Crit Care Med 182:62–72PubMedCrossRefGoogle Scholar
  8. Chotirmall SH, Smith SG, Gunaratnam C et al (2012) Effect of estrogen on pseudomonas mucoidy and exacerbations in cystic fibrosis. N Engl J Med 366:1978–1986PubMedCrossRefGoogle Scholar
  9. Cinel I, Dellinger RP (2007) Advances in pathogenesis and management of sepsis. Curr Opin Infect Dis 20:345–352PubMedCrossRefGoogle Scholar
  10. Ciofu O, Riis B, Pressler T et al (2005) Occurrence of hypermutable Pseudomonas aeruginosa in cystic fibrosis patients is associated with the oxidative stress caused by chronic lung inflammation. Antimicrob Agents Chemother 49:2276–2282PubMedPubMedCentralCrossRefGoogle Scholar
  11. Clamens T, Rosay T, Crépin A et al (2017) The aliphatic amidase AmiE is involved in regulation of Pseudomonas aeruginosa virulence. Sci Rep 7:41178PubMedPubMedCentralCrossRefGoogle Scholar
  12. Cole JN, Nizet V (2016) Bacterial evasion of host antimicrobial peptide defenses. Microbiol Spectr 4:413–443Google Scholar
  13. Cosgrove S, Chotirmall SH, Greene CM et al (2011) Pulmonary proteases in the cystic fibrosis lung induce interleukin 8 expression from bronchial epithelial cells via a heme/meprin/epidermal growth factor receptor/Toll-like receptor pathway. J Biol Chem 286:7692–7704PubMedCrossRefGoogle Scholar
  14. Costerton W, Veeh R, Shirtliff M et al (2003) The application of biofilm science to the study and control of chronic bacterial infections. J Clin Invest 112:1466–1477PubMedPubMedCentralCrossRefGoogle Scholar
  15. Crousilles A, Maunders E, Bartlett S et al (2015) Which microbial factors really are important in Pseudomonas aeruginosa infections? Future Microbiol 10:1825–1836PubMedCrossRefGoogle Scholar
  16. Deng HP, Chai JK (2009) The effects and mechanisms of insulin on systemic inflammatory response and immune cells in severe trauma, burn injury, and sepsis. Int Immunopharmacol 9:1251–1259PubMedCrossRefGoogle Scholar
  17. Deng JC, Cheng G, Newstead MW et al (2006) Sepsis-induced suppression of lung innate immunity is mediated by IRAK-M. J Clin Invest 116:2532–2542PubMedPubMedCentralGoogle Scholar
  18. Dietrich LE, Teal TK, Price-Whelan A et al (2008) Redox-active antibiotics control gene expression and community behavior in divergent bacteria. Science 321:1203–1206PubMedPubMedCentralCrossRefGoogle Scholar
  19. Diggle SP, Matthijs S, Wright VJ et al (2007) The Pseudomonas aeruginosa 4-quinolone signal molecules HHQ and PQS play multifunctional roles in quorum sensing and iron entrapment. Chem Biol 14:87–96PubMedCrossRefGoogle Scholar
  20. Djonovic S, Urbach JM, Drenkard E et al (2013) Trehalose biosynthesis promotes Pseudomonas aeruginosa pathogenicity in plants. PLoS Pathog 9:e1003217PubMedPubMedCentralCrossRefGoogle Scholar
  21. Elenkov IJ (2007) Effects of catecholamines on the immune response. NeuroImmune Biol 7:189–206CrossRefGoogle Scholar
  22. Elkins CA, Mullis LB (2006) Mammalian steroid hormones are substrates for the major RND- and MFS-type tripartite multidrug efflux pumps of Escherichia coli. J Bacteriol 188:1191–1195PubMedPubMedCentralCrossRefGoogle Scholar
  23. Fargier E, Mac Aogáin M, Mooij MJ et al (2012) MexT functions as a redox-responsive regulator modulating disulfide stress resistance in Pseudomonas aeruginosa. J Bacteriol 194:3502–3511PubMedPubMedCentralCrossRefGoogle Scholar
  24. Flierl MA, Rittirsch D, Huber-Lang M et al (2008) Catecholamines-crafty weapons in the inflammatory arsenal of immune/inflammatory cells or opening pandora’s box? Mol Med 14:195–204PubMedGoogle Scholar
  25. Foo YZ, Nakagawa S, Rhodes G et al (2017) The effects of sex hormones on immune function: a meta-analysis. Biol Rev Camb Philos Soc 92:551–571PubMedCrossRefGoogle Scholar
  26. Franchi L, Munoz-Planillo R, Nunez G (2012) Sensing and reacting to microbes through the inflammasomes. Nat Immunol 13:325–332PubMedPubMedCentralCrossRefGoogle Scholar
  27. Freestone P (2013) Communication between bacteria and their hosts. Scientifica 2013:361073PubMedPubMedCentralCrossRefGoogle Scholar
  28. Freestone PP, Hirst RA, Sandrini SM et al (2012) Pseudomonas aeruginosa-catecholamine inotrope interactions: a contributory factor in the development of ventilator-associated pneumonia? Chest 142:1200–1210PubMedCrossRefGoogle Scholar
  29. Garcia-Gomez E, Gonzalez-Pedrajo B, Camacho-Arroyo I (2013) Role of sex steroid hormones in bacterial-host interactions. Biomed Res Int 2013:928290PubMedCrossRefGoogle Scholar
  30. Gein SV (2014) Dynorphins in regulation of immune system functions. Biochemistry 79:397–405PubMedGoogle Scholar
  31. Gellatly SL, Hancock RE (2013) Pseudomonas aeruginosa: new insights into pathogenesis and host defenses. Pathog Dis 67:159–173PubMedCrossRefGoogle Scholar
  32. Ghafoor A, Hay ID, Rehm BH (2011) Role of exopolysaccharides in Pseudomonas aeruginosa biofilm formation and architecture. Appl Environ Microbiol 77:5238–5246PubMedPubMedCentralCrossRefGoogle Scholar
  33. Gibson RL, Burns JL, Ramsey BW (2003) Pathophysiology and management of pulmonary infections in cystic fibrosis. Am J Respir Crit Care Med 168:918–951PubMedCrossRefGoogle Scholar
  34. Gómez MI, Prince A (2007) Opportunistic infections in lung disease: Pseudomonas infections in cystic fibrosis. Curr Opin Pharmacol 7:244–251PubMedCrossRefGoogle Scholar
  35. Grisanti LA, Woster AP, Dahlman J et al (2011) Alpha1-adrenergic receptors positively regulate Toll-like receptor cytokine production from human monocytes and macrophages. J Pharmacol Exp Ther 338:648–657PubMedPubMedCentralCrossRefGoogle Scholar
  36. Guttenplan SB, Kearns DB (2013) Regulation of flagellar motility during biofilm formation. FEMS Microbiol Rev 37:849–871PubMedPubMedCentralCrossRefGoogle Scholar
  37. Hall S, McDermott C, Anoopkumar-Dukie S et al (2016) Cellular effects of pyocyanin, a secreted virulence factor of Pseudomonas aeruginosa. Toxins 8(8):236. PubMedCentralCrossRefGoogle Scholar
  38. Harness-Brumley CL, Elliott AC, Rosenbluth DB et al (2014) Gender differences in outcomes of patients with cystic fibrosis. J Womens Health 23:1012–1020CrossRefGoogle Scholar
  39. Hartl D, Griese M, Kappler M et al (2006) Pulmonary T(H)2 response in Pseudomonas aeruginosa-infected patients with cystic fibrosis. J Allergy Clin Immunol 117:204–211PubMedCrossRefGoogle Scholar
  40. Hector A, Schäfer H, Pöschel S et al (2015) Regulatory T-cell impairment in cystic fibrosis patients with chronic pseudomonas infection. Am J Respir Crit Care Med 191:914–923PubMedCrossRefGoogle Scholar
  41. Herr N, Bode C, Duerschmied D (2017) The effects of serotonin in immune cells. Front Cardiovasc Med 4:48PubMedPubMedCentralCrossRefGoogle Scholar
  42. Hughes DT, Sperandio V (2008) Inter-kingdom signalling: communication between bacteria and their hosts. Nat Rev Microbiol 6:111–120PubMedPubMedCentralCrossRefGoogle Scholar
  43. Jansen ASP, Van Nguyen X, Karpitskiy V et al (1995) Central command neurons of the sympathetic nervous system: basis of the fight-or-flight response. Science 270:644–646PubMedCrossRefGoogle Scholar
  44. Jensen PO, Givskov M, Bjarnsholt T et al (2010) The immune system vs. Pseudomonas aeruginosa biofilms. FEMS Immunol Med Microbiol 59:292–305PubMedCrossRefGoogle Scholar
  45. Jimenez PN, Koch G, Thompson JA et al (2012) The multiple signaling systems regulating virulence in Pseudomonas aeruginosa. Microbiol Mol Biol Rev 76:46–65PubMedCrossRefGoogle Scholar
  46. Jones RN (2010) Microbial etiologies of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. Clin Infect Dis 51(Suppl 1):S81–S87PubMedCrossRefGoogle Scholar
  47. Kiseleva E, Novik G (2015) Role of type III secretory system and related exotoxins in infections induced by an opportunistic pathogen Pseudomonas aeruginosa. In: Méndez-Vilas A (ed) The battle against microbial pathogens: basic science, technological advances and educational programs. FORMATEX microbiology series N 5, vol 2. pp 733–744Google Scholar
  48. Klein SL, Flanagan KL (2016) Sex differences in immune responses. Nat Rev Immunol 16:626–638PubMedCrossRefGoogle Scholar
  49. Knecht LD, O’Connor G, Mittal R et al (2016) Serotonin activates bacterial quorum sensing and enhances the virulence of Pseudomonas aeruginosa in the host. EBioMedicine 9:161–169PubMedPubMedCentralCrossRefGoogle Scholar
  50. Lagoumintzis G, Christofidou M, Dimitracopoulos G et al (2003) Pseudomonas aeruginosa slime glycolipoprotein is a potent stimulant of tumor necrosis factor alpha gene expression and activation of transcription activators nuclear factor κB and activator protein 1 in human monocytes. Infect Immun 71:4614–4622PubMedPubMedCentralCrossRefGoogle Scholar
  51. Lagoumintzis G, Xaplanteri P, Dimitracopoulos G et al (2008) TNF-alpha induction by Pseudomonas aeruginosa lipopolysaccharide or slime-glycolipoprotein in human monocytes is regulated at the level of Mitogen-activated Protein Kinase activity: a distinct role of Toll-like receptor 2 and 4. Scand J Immunol 67:193–203PubMedCrossRefGoogle Scholar
  52. Lavoie EG, Wangdi T, Kazmierczak BI (2011) Innate immune responses to Pseudomonas aeruginosa infection. Microbes Infect 13:1133–1145PubMedPubMedCentralCrossRefGoogle Scholar
  53. Lecaille F, Lalmanach G, Andrault PM (2016) Antimicrobial proteins and peptides in human lung diseases: a friend and foe partnership with host proteases. Biochimie 122:151–168PubMedCrossRefGoogle Scholar
  54. Lee J, Zhang L (2015) The hierarchy quorum sensing network in Pseudomonas aeruginosa. Protein Cell 6:26–41PubMedCrossRefGoogle Scholar
  55. Leone M, Textoris J, Capo C and Mege J-L (2012) Sex hormones and bacterial infections. In: Dubey R (ed) Sex hormones. InTech. Accessed 8 July 2017
  56. Leung JM, Tiew PY, Mac Aogáin M et al (2017) The role of acute and chronic respiratory colonization and infections in the pathogenesis of COPD. Respirology 22:634–650PubMedCrossRefGoogle Scholar
  57. Li W, Lyte M, Freestone PP et al (2009) Norepinephrine represses the expression of toxA and the siderophore genes in Pseudomonas aeruginosa. FEMS Microbiol Lett 299:100–109PubMedPubMedCentralCrossRefGoogle Scholar
  58. Lore NI, Cigana C, Riva C et al (2016) IL-17A impairs host tolerance during airway chronic infection by Pseudomonas aeruginosa. Sci Rep 6:25937PubMedPubMedCentralCrossRefGoogle Scholar
  59. Lyte M (2013) Microbial endocrinology in the microbiome-gut-brain axis: how bacterial production and utilization of neurochemicals influence behavior. PLoS Pathog 9:e1003726PubMedPubMedCentralCrossRefGoogle Scholar
  60. Lyte M, Ernst S (1992) Catecholamine induced growth of gram negative bacteria. Life Sci 50:203–212PubMedCrossRefGoogle Scholar
  61. Mahdy AM, Webster NR (2011) Histamine and antihistamines. Anaesth Intensive Care Med 12:324–329CrossRefGoogle Scholar
  62. Maseda H, Sawada I, Saito K et al (2004) Enhancement of the mexAB-oprM efflux pump expression by a quorum-sensing autoinducer and its cancellation by a regulator, MexT, of the mexEF-oprN efflux pump operon in Pseudomonas aeruginosa. Antimicrob Agents Chemother 48:1320–1328PubMedPubMedCentralCrossRefGoogle Scholar
  63. Miao EA, Mao DP, Yudkovsky N et al (2010) Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome. Proc Natl Acad Sci USA 107:3076–3080PubMedPubMedCentralCrossRefGoogle Scholar
  64. Mogensen TH (2009) Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev 22:240–273PubMedPubMedCentralCrossRefGoogle Scholar
  65. Mulcahy LR, Isabella VM, Lewis K (2014) Pseudomonas aeruginosa biofilms in disease. Microb Ecol 68:1–12PubMedCrossRefGoogle Scholar
  66. Mund A, Diggle SP, Harrison F (2017) The fitness of Pseudomonas aeruginosa quorum sensing signal cheats is influenced by the diffusivity of the environment. MBio 8(3):e00353-17. PubMedPubMedCentralGoogle Scholar
  67. Murray MA, Chotirmall SH (2015) The impact of immunosenescence on pulmonary disease. Mediators Inflamm 2015:692546PubMedPubMedCentralCrossRefGoogle Scholar
  68. Nakanishi K, Tajima F, Itoh H et al (1999) Expression of C-type natriuretic peptide during development of rat lung. Am J Physiol 277(5 Pt 1):L996–L1002PubMedGoogle Scholar
  69. O’Loughlin CT, Miller LC, Siryaporn A et al (2013) A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation. Proc Natl Acad Sci USA 110:17981–17986PubMedPubMedCentralCrossRefGoogle Scholar
  70. Ortona E, Delunardo F, Maselli A et al (2015) Sex hormones and gender disparity in immunity and autoimmunity. Italian J Gender Specific Med 1:45–50Google Scholar
  71. Papenfort K, Bassler BL (2016) Quorum sensing signal-response systems in Gram-negative bacteria. Nat Rev Microbiol 14:576–588PubMedPubMedCentralCrossRefGoogle Scholar
  72. Parkins MD, Gregson DB, Pitout JD et al (2010) Population-based study of the epidemiology and the risk factors for Pseudomonas aeruginosa bloodstream infection. Infection 38:25–32PubMedCrossRefGoogle Scholar
  73. Peek ME, Bhatnagar A, McCarty NA et al (2012) Pyoverdine, the major siderophore in Pseudomonas aeruginosa, evades NGAL recognition. Interdiscip Perspect Infect Dis 2012:843509PubMedPubMedCentralCrossRefGoogle Scholar
  74. Pu Q, Gan C, Li R et al (2017) Atg7 Deficiency intensifies inflammasome activation and pyroptosis in Pseudomonas sepsis. J Immunol 198:3205–3213PubMedCrossRefGoogle Scholar
  75. Quick J, Cumley N, Wearn CM et al (2014) Seeking the source of Pseudomonas aeruginosa infections in a recently opened hospital: an observational study using whole-genome sequencing. BMJ Open 4:e006278PubMedPubMedCentralCrossRefGoogle Scholar
  76. Rabin N, Zheng Y, Opoku-Temeng C et al (2015) Biofilm formation mechanisms and targets for developing antibiofilm agents. Future Med Chem 7:493–512PubMedCrossRefGoogle Scholar
  77. Rada B (2017) Interactions between neutrophils and Pseudomonas aeruginosa in cystic fibrosis. Pathogens 6(1):E10. PubMedCrossRefGoogle Scholar
  78. Rosay T, Bazire A, Diaz S et al. (2015) Pseudomonas aeruginosa expresses a functional human natriuretic peptide receptor ortholog: involvement in biofilm formation. MBio 6(4):e01033-15. PubMedPubMedCentralCrossRefGoogle Scholar
  79. Sakhtah H, Koyama L, Zhang Y et al (2016) The Pseudomonas aeruginosa efflux pump MexGHI-OpmD transports a natural phenazine that controls gene expression and biofilm development. Proc Natl Acad Sci USA 113:E3538–E3547PubMedPubMedCentralCrossRefGoogle Scholar
  80. Schwarzer C (2009) 30 years of dynorphins—new insights on their functions in neuropsychiatric diseases. Pharmacol Ther 123:353–370PubMedPubMedCentralCrossRefGoogle Scholar
  81. Shajib MS, Khan WI (2015) The role of serotonin and its receptors in activation of immune responses and inflammation. Acta Physiol 213:561–574CrossRefGoogle Scholar
  82. Silva Filho LV, Ferreira Fde A, Reis FJ et al (2013) Pseudomonas aeruginosa infection in patients with cystic fibrosis: scientific evidence regarding clinical impact, diagnosis, and treatment. J Bras Pneumol 39:495–512PubMedCrossRefGoogle Scholar
  83. Singh PK, Parsek MR, Greenberg EP et al (2002) A component of innate immunity prevents bacterial biofilm development. Nature 417:552–555PubMedCrossRefGoogle Scholar
  84. Skerrett SJ, Liggitt HD, Hajjar AM et al (2004) Cutting Edge: Myeloid differentiation factor 88 is essential for pulmonary host defense against Pseudomonas aeruginosa but not Staphylococcus aureus. J Immunol 172:3377–3381PubMedCrossRefGoogle Scholar
  85. Sun J, Deng Z, Yan A (2014) Bacterial multidrug efflux pumps: mechanisms, physiology and pharmacological exploitations. Biochem Biophys Res Commun 453:254–267PubMedCrossRefGoogle Scholar
  86. Tateda K, Ishii Y, Horikawa M et al (2003) The Pseudomonas aeruginosa autoinducer N-3-Oxododecanoyl homoserine lactone accelerates apoptosis in macrophages and neutrophils. Infect Immun 71:5785–5793PubMedPubMedCentralCrossRefGoogle Scholar
  87. Tian ZX, Fargier E, Mac Aogain M et al (2009) Transcriptome profiling defines a novel regulon modulated by the LysR-type transcriptional regulator MexT in Pseudomonas aeruginosa. Nucleic Acids Res 37:7546–7559PubMedPubMedCentralCrossRefGoogle Scholar
  88. Tiringer K, Treis A, Fucik P et al (2013) A Th17- and Th2-skewed cytokine profile in cystic fibrosis lungs represents a potential risk factor for Pseudomonas aeruginosa infection. Am J Respir Crit Care Med 187:621–629PubMedCrossRefGoogle Scholar
  89. Tredget EE, Shankowsky HA, Rennie R et al (2004) Pseudomonas infections in the thermally injured patient. Burns 30:3–26PubMedCrossRefGoogle Scholar
  90. Trigunaite A, Dimo J, Jørgensen TN (2015) Suppressive effects of androgens on the immune system. Cell Immunol 294:87–94PubMedCrossRefGoogle Scholar
  91. Tumbarello M, Repetto E, Trecarichi EM et al (2011) Multidrug-resistant Pseudomonas aeruginosa bloodstream infections: risk factors and mortality. Epidemiol Infect 139:1740–1749PubMedCrossRefGoogle Scholar
  92. Valentino RJ, Van Bockstaele E (2015) Endogenous opioids: the downside of opposing stress. Neurobiol Stress 1:23–32PubMedCrossRefGoogle Scholar
  93. Veesenmeyer JL, Hauser AR, Lisboa T et al (2009) Pseudomonas aeruginosa virulence and therapy: evolving translational strategies. Crit Care Med 37:1777–1786PubMedPubMedCentralCrossRefGoogle Scholar
  94. Veron W, Lesouhaitier O, Pennanec X et al (2007) Natriuretic peptides affect Pseudomonas aeruginosa and specifically modify lipopolysaccharide biosynthesis. FEBS J 274:5852–5864PubMedCrossRefGoogle Scholar
  95. Visca P, Imperi F, Lamont IL (2007) Pyoverdine siderophores: from biogenesis to biosignificance. Trends Microbiol 15:22–30PubMedCrossRefGoogle Scholar
  96. Vital-Lopez FG, Reifman J, Wallqvist A (2015) Biofilm formation mechanisms of Pseudomonas aeruginosa predicted via genome-scale kinetic models of bacterial metabolism. PLoS Comput Biol 11:e1004452PubMedPubMedCentralCrossRefGoogle Scholar
  97. Vogel G (2017) Meet WHO’s dirty dozen: the 12 bacteria for which new drugs are most urgently needed. Science Magazine, 27 Feb 2017.
  98. vom Steeg LG, Klein SL (2017) Sex steroids mediate bidirectional interactions between hosts and microbes. Horm Behav 88:45–51CrossRefGoogle Scholar
  99. Wang Y, Cela E, Gagnon S et al (2010) Estrogen aggravates inflammation in Pseudomonas aeruginosa pneumonia in cystic fibrosis mice. Respir Res 11:166PubMedPubMedCentralCrossRefGoogle Scholar
  100. Watters C, Everett JA, Haley C et al (2014) Insulin treatment modulates the host immune system to enhance Pseudomonas aeruginosa wound biofilms. Infect Immun 82:92–100PubMedPubMedCentralCrossRefGoogle Scholar
  101. Weiner LM, Webb AK, Limbago B et al (2016) Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2011–2014. Infect Control Hosp Epidemiol 37:1288–1301PubMedCrossRefGoogle Scholar
  102. Williams IR, Parkos CA (2007) Colonic neutrophils in inflammatory bowel disease: double-edged swords of the innate immune system with protective and destructive capacity. Gastroenterology 133:2049–2052PubMedCrossRefGoogle Scholar
  103. Wisplinghoff H, Bischoff T, Tallent SM et al (2004) Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 39:309–317PubMedCrossRefGoogle Scholar
  104. Xaplanteri P, Lagoumintzis G, Dimitracopoulos G et al (2009) Synergistic regulation of Pseudomonas aeruginosa-induced cytokine production in human monocytes by mannose receptor and TLR2. Eur J Immunol 39:730–740PubMedCrossRefGoogle Scholar
  105. Xu X, Zhang H, Song Y et al (2012) Strain-dependent induction of neutrophil histamine production and cell death by Pseudomonas aeruginosa. J Leukoc Biol 91:275–284PubMedPubMedCentralCrossRefGoogle Scholar
  106. Zaborina O, Lepine F, Xiao G et al (2007) Dynorphin activates quorum sensing quinolone signaling in Pseudomonas aeruginosa. PLoS Pathog 3:e35PubMedPubMedCentralCrossRefGoogle Scholar
  107. Zhang Z, Louboutin JP, Weiner DJ et al (2005) Human airway epithelial cells sense Pseudomonas aeruginosa infection via recognition of flagellin by Toll-like receptor 5. Infect Immun 73:7151–7160PubMedPubMedCentralCrossRefGoogle Scholar
  108. Zhu J, Yamane H, Paul WE (2010) Differentiation of effector CD4 T cell populations. Annu Rev Immunol 28:445–489PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2018

Authors and Affiliations

  1. 1.Translational Respiratory Research Laboratory, Lee Kong Chian School of MedicineNanyang Technological UniversitySingaporeSingapore

Personalised recommendations