1887

Abstract

The human body is constantly challenged by a variety of commensal and pathogenic micro-organisms that trigger the immune system. Central in the first line of defence is the pattern-recognition receptor (PRR)-induced stimulation of the NFκB pathway, leading to NFκB activation. The subsequent production of pro-inflammatory cytokines and/or antimicrobial peptides results in recruitment of professional phagocytes and bacterial clearance. To overcome this, bacteria have developed mechanisms for targeted interference in every single step in the PRR–NFκB pathway to dampen host inflammatory responses. This review aims to briefly overview the PRR–NFκB pathway in relation to the immune response and give examples of the diverse bacterial evasion mechanisms including changes in the bacterial surface, decoy production and injection of effector molecules. Targeted regulation of inflammatory responses is needed and bacterial molecules developed for immune evasion could provide future anti-inflammatory agents.

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2013-10-01
2020-01-19
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References

  1. Abeyta M., Hardy G. G., Yother J.. ( 2003;). Genetic alteration of capsule type but not PspA type affects accessibility of surface-bound complement and surface antigens of Streptococcus pneumoniae . Infect Immun71:218–225 [CrossRef][PubMed]
    [Google Scholar]
  2. Albiger B., Sandgren A., Katsuragi H., Meyer-Hoffert U., Beiter K., Wartha F., Hornef M., Normark S., Normark B. H.. ( 2005;). Myeloid differentiation factor 88-dependent signalling controls bacterial growth during colonization and systemic pneumococcal disease in mice. Cell Microbiol7:1603–1615 [CrossRef][PubMed]
    [Google Scholar]
  3. Arbibe L., Kim D. W., Batsche E., Pedron T., Mateescu B., Muchardt C., Parsot C., Sansonetti P. J.. ( 2007;). An injected bacterial effector targets chromatin access for transcription factor NFκB to alter transcription of host genes involved in immune responses. Nat Immunol8:47–56 [CrossRef][PubMed]
    [Google Scholar]
  4. Ashida H., Kim M., Schmidt-Supprian M., Ma A., Ogawa M., Sasakawa C.. ( 2010;). A bacterial E3 ubiquitin ligase IpaH9.8 targets NEMO/IKKγ to dampen the host NFκB-mediated inflammatory response. Nat Cell Biol12:66–73, 1–9 [CrossRef][PubMed]
    [Google Scholar]
  5. Bardoel B. W., Vos R., Bouman T., Aerts P. C., Bestebroer J., Huizinga E. G., Brondijk T. H., van Strijp J. A., de Haas C. J.. ( 2012;). Evasion of Toll-like receptor 2 activation by staphylococcal superantigen-like protein 3. J Mol Med (Berl)90:1109–1120 [CrossRef][PubMed]
    [Google Scholar]
  6. Barrow A. D., Trowsdale J.. ( 2006;). You say ITAM and I say ITIM, let’s call the whole thing off: the ambiguity of immunoreceptor signalling. Eur J Immunol36:1646–1653 [CrossRef][PubMed]
    [Google Scholar]
  7. Baruch K., Gur-Arie L., Nadler C., Koby S., Yerushalmi G., Ben-Neriah Y., Yogev O., Shaulian E., Guttman C.. & other authors ( 2011;). Metalloprotease type III effectors that specifically cleave JNK and NF-κB. EMBO J30:221–231 [CrossRef][PubMed]
    [Google Scholar]
  8. Bestebroer J., De Haas C. J., Van Strijp J. A.. ( 2010;). How microorganisms avoid phagocyte attraction. FEMS Microbiol Rev34:395–414 [CrossRef][PubMed]
    [Google Scholar]
  9. Biswas A., Wilmanski J., Forsman H., Hrncir T., Hao L., Tlaskalova-Hogenova H., Kobayashi K. S.. ( 2011;). Negative regulation of Toll-like receptor signaling plays an essential role in homeostasis of the intestine. Eur J Immunol41:182–194 [CrossRef][PubMed]
    [Google Scholar]
  10. Burns K., Janssens S., Brissoni B., Olivos N., Beyaert R., Tschopp J.. ( 2003;). Inhibition of interleukin 1 receptor/Toll-like receptor signaling through the alternatively spliced, short form of MyD88 is due to its failure to recruit IRAK-4. J Exp Med197:263–268 [CrossRef][PubMed]
    [Google Scholar]
  11. Carpenter S., O’Neill L. A.. ( 2007;). How important are Toll-like receptors for antimicrobial responses?. Cell Microbiol9:1891–1901 [CrossRef][PubMed]
    [Google Scholar]
  12. Casanova J. L., Abel L., Quintana-Murci L.. ( 2011;). Human TLRs and IL-1Rs in host defense: natural insights from evolutionary, epidemiological, and clinical genetics. Annu Rev Immunol29:447–491 [CrossRef][PubMed]
    [Google Scholar]
  13. Chen Z. J.. ( 2005;). Ubiquitin signalling in the NF-κB pathway. Nat Cell Biol7:758–765 [CrossRef][PubMed]
    [Google Scholar]
  14. Chen L. F., Mu Y., Greene W. C.. ( 2002;). Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF-κB. EMBO J21:6539–6548 [CrossRef][PubMed]
    [Google Scholar]
  15. Cigana C., Curcurù L., Leone M. R., Ieranò T., Lorè N. I., Bianconi I., Silipo A., Cozzolino F., Lanzetta R.. & other authors ( 2009;). Pseudomonas aeruginosa exploits lipid A and muropeptides modification as a strategy to lower innate immunity during cystic fibrosis lung infection. PLoS ONE4:e8439 [CrossRef][PubMed]
    [Google Scholar]
  16. Cirl C., Wieser A., Yadav M., Duerr S., Schubert S., Fischer H., Stappert D., Wantia N., Rodriguez N.. & other authors ( 2008;). Subversion of Toll-like receptor signaling by a unique family of bacterial Toll/interleukin-1 receptor domain-containing proteins. Nat Med14:399–406 [CrossRef][PubMed]
    [Google Scholar]
  17. Collier-Hyams L. S., Zeng H., Sun J., Tomlinson A. D., Bao Z. Q., Chen H., Madara J. L., Orth K., Neish A. S.. ( 2002;). Cutting edge: Salmonella AvrA effector inhibits the key proinflammatory, anti-apoptotic NF-κB pathway. J Immunol169:2846–2850[PubMed][CrossRef]
    [Google Scholar]
  18. Deshmukh H. S., Hamburger J. B., Ahn S. H., McCafferty D. G., Yang S. R., Fowler V. G. Jr. ( 2009;). Critical role of NOD2 in regulating the immune response to Staphylococcus aureus . Infect Immun77:1376–1382 [CrossRef][PubMed]
    [Google Scholar]
  19. Domon H., Honda T., Oda T., Yoshie H., Yamazaki K.. ( 2008;). Early and preferential induction of IL-1 receptor-associated kinase-M in THP-1 cells by LPS derived from Porphyromonas gingivalis . J Leukoc Biol83:672–679 [CrossRef][PubMed]
    [Google Scholar]
  20. Fraser J. D., Proft T.. ( 2008;). The bacterial superantigen and superantigen-like proteins. Immunol Rev225:226–243 [CrossRef][PubMed]
    [Google Scholar]
  21. Gao X., Wan F., Mateo K., Callegari E., Wang D., Deng W., Puente J., Li F., Chaussee M. S.. & other authors ( 2009;). Bacterial effector binding to ribosomal protein s3 subverts NF-κB function. PLoS Pathog5:e1000708 [CrossRef][PubMed]
    [Google Scholar]
  22. Ge J., Xu H., Li T., Zhou Y., Zhang Z., Li S., Liu L., Shao F.. ( 2009;). A Legionella type IV effector activates the NF-κB pathway by phosphorylating the IκB family of inhibitors. Proc Natl Acad Sci U S A106:13725–13730 [CrossRef][PubMed]
    [Google Scholar]
  23. Gunn J. S., Ernst R. K.. ( 2007;). The structure and function of Francisella lipopolysaccharide. Ann N Y Acad Sci1105:202–218 [CrossRef][PubMed]
    [Google Scholar]
  24. Hajishengallis G., Wang M., Liang S., Triantafilou M., Triantafilou K.. ( 2008;). Pathogen induction of CXCR4/TLR2 cross-talk impairs host defense function. Proc Natl Acad Sci U S A105:13532–13537 [CrossRef][PubMed]
    [Google Scholar]
  25. Han J., Ulevitch R. J.. ( 2005;). Limiting inflammatory responses during activation of innate immunity. Nat Immunol6:1198–1205 [CrossRef][PubMed]
    [Google Scholar]
  26. Hoebe K., Georgel P., Rutschmann S., Du X., Mudd S., Crozat K., Sovath S., Shamel L., Hartung T.. & other authors ( 2005;). CD36 is a sensor of diacylglycerides. Nature433:523–527 [CrossRef][PubMed]
    [Google Scholar]
  27. Hoshino K., Takeuchi O., Kawai T., Sanjo H., Ogawa T., Takeda Y., Takeda K., Akira S.. ( 1999;). Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J Immunol162:3749–3752[PubMed]
    [Google Scholar]
  28. Huang T. T., Kudo N., Yoshida M., Miyamoto S.. ( 2000;). A nuclear export signal in the N-terminal regulatory domain of IκBα controls cytoplasmic localization of inactive NF-κB/IκBα complexes. Proc Natl Acad Sci U S A97:1014–1019 [CrossRef][PubMed]
    [Google Scholar]
  29. Janssens S., Burns K., Tschopp J., Beyaert R.. ( 2002;). Regulation of interleukin-1- and lipopolysaccharide-induced NF-κB activation by alternative splicing of MyD88. Curr Biol12:467–471 [CrossRef][PubMed]
    [Google Scholar]
  30. Jeong E., Lee J. Y.. ( 2011;). Intrinsic and extrinsic regulation of innate immune receptors. Yonsei Med J52:379–392 [CrossRef][PubMed]
    [Google Scholar]
  31. Jiang X., Chen Z. J.. ( 2012;). The role of ubiquitylation in immune defence and pathogen evasion. Nat Rev Immunol12:35–48[PubMed]
    [Google Scholar]
  32. Kawasaki K., Ernst R. K., Miller S. I.. ( 2004;). 3-O-deacylation of lipid A by PagL, a PhoP/PhoQ-regulated deacylase of Salmonella typhimurium, modulates signaling through Toll-like receptor 4. J Biol Chem279:20044–20048 [CrossRef][PubMed]
    [Google Scholar]
  33. Kelly D., Campbell J. I., King T. P., Grant G., Jansson E. A., Coutts A. G., Pettersson S., Conway S.. ( 2004;). Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-γ and RelA. Nat Immunol5:104–112 [CrossRef][PubMed]
    [Google Scholar]
  34. Kersse K., Bertrand M. J., Lamkanfi M., Vandenabeele P.. ( 2011;). NOD-like receptors and the innate immune system: coping with danger, damage and death. Cytokine Growth Factor Rev22:257–276 [CrossRef][PubMed]
    [Google Scholar]
  35. Kim D. W., Lenzen G., Page A. L., Legrain P., Sansonetti P. J., Parsot C.. ( 2005;). The Shigella flexneri effector OspG interferes with innate immune responses by targeting ubiquitin-conjugating enzymes. Proc Natl Acad Sci U S A102:14046–14051 [CrossRef][PubMed]
    [Google Scholar]
  36. Kissner T. L., Moisan L., Mann E., Alam S., Ruthel G., Ulrich R. G., Rebek M., Rebek J. Jr, Saikh K. U.. ( 2011;). A small molecule that mimics the BB-loop in the Toll interleukin-1 (IL-1) receptor domain of MyD88 attenuates staphylococcal enterotoxin B-induced pro-inflammatory cytokine production and toxicity in mice. J Biol Chem286:31385–31396 [CrossRef][PubMed]
    [Google Scholar]
  37. Kumar H., Kawai T., Akira S.. ( 2009;). Pathogen recognition in the innate immune response. Biochem J420:1–16 [CrossRef][PubMed]
    [Google Scholar]
  38. Lamb A., Yang X. D., Tsang Y. H., Li J. D., Higashi H., Hatakeyama M., Peek R. M., Blanke S. R., Chen L. F.. ( 2009;). Helicobacter pylori CagA activates NF-κB by targeting TAK1 for TRAF6-mediated Lys 63 ubiquitination. EMBO Rep10:1242–1249 [CrossRef][PubMed]
    [Google Scholar]
  39. Le Negrate G., Faustin B., Welsh K., Loeffler M., Krajewska M., Hasegawa P., Mukherjee S., Orth K., Krajewski S.. & other authors ( 2008;). Salmonella secreted factor L deubiquitinase of Salmonella typhimurium inhibits NF-κB, suppresses IκBα ubiquitination and modulates innate immune responses. J Immunol180:5045–5056[PubMed][CrossRef]
    [Google Scholar]
  40. Lee M. S., Kim Y. J.. ( 2007;). Signaling pathways downstream of pattern-recognition receptors and their cross talk. Annu Rev Biochem76:447–480 [CrossRef][PubMed]
    [Google Scholar]
  41. Lee Y. J., Choi H. J., Kang T. W., Kim H. O., Chung M. J., Park Y. M.. ( 2008;). CBT-SL5, a bacteriocin from Enterococcus faecalis, suppresses the expression of interleukin-8 induced by Propionibacterium acnes in cultured human keratinocytes. J Microbiol Biotechnol18:1308–1316[PubMed]
    [Google Scholar]
  42. Leendertse M., Willems R. J., Giebelen I. A., van den Pangaart P. S., Wiersinga W. J., de Vos A. F., Florquin S., Bonten M. J., van der Poll T.. ( 2008;). TLR2-dependent MyD88 signaling contributes to early host defense in murine Enterococcus faecium peritonitis. J Immunol180:4865–4874[PubMed][CrossRef]
    [Google Scholar]
  43. Li Q., Verma I. M.. ( 2002;). NF-kappaB regulation in the immune system. Nat Rev Immunol2:725–734 [CrossRef][PubMed]
    [Google Scholar]
  44. Li C., Zienkiewicz J., Hawiger J.. ( 2005;). Interactive sites in the MyD88 Toll/interleukin (IL) 1 receptor domain responsible for coupling to the IL1β signaling pathway. J Biol Chem280:26152–26159 [CrossRef][PubMed]
    [Google Scholar]
  45. Liu M., Haenssler E., Uehara T., Losick V. P., Park J. T., Isberg R. R.. ( 2012;). The Legionella pneumophila EnhC protein interferes with immunostimulatory muramyl peptide production to evade innate immunity. Cell Host Microbe12:166–176 [CrossRef][PubMed]
    [Google Scholar]
  46. Losick V. P., Haenssler E., Moy M. Y., Isberg R. R.. ( 2010;). LnaB: a Legionella pneumophila activator of NF-κB. Cell Microbiol12:1083–1097 [CrossRef][PubMed]
    [Google Scholar]
  47. Madan-Lala R., Peixoto K. V., Re F., Rengarajan J.. ( 2011;). Mycobacterium tuberculosis Hip1 dampens macrophage proinflammatory responses by limiting toll-like receptor 2 activation. Infect Immun79:4828–4838 [CrossRef][PubMed]
    [Google Scholar]
  48. March C., Moranta D., Regueiro V., Llobet E., Tomás A., Garmendia J., Bengoechea J. A.. ( 2011;). Klebsiella pneumoniae outer membrane protein A is required to prevent the activation of airway epithelial cells. J Biol Chem286:9956–9967 [CrossRef][PubMed]
    [Google Scholar]
  49. Mittal R., Peak-Chew S. Y., McMahon H. T.. ( 2006;). Acetylation of MEK2 and I κB kinase (IKK) activation loop residues by YopJ inhibits signaling. Proc Natl Acad Sci U S A103:18574–18579 [CrossRef][PubMed]
    [Google Scholar]
  50. Motta J. P., Bermúdez-Humarán L. G., Deraison C., Martin L., Rolland C., Rousset P., Boue J., Dietrich G., Chapman K.. & other authors ( 2012;). Food-grade bacteria expressing elafin protect against inflammation and restore colon homeostasis. Sci Transl Med4:158ra144 [CrossRef][PubMed]
    [Google Scholar]
  51. Mühlen S., Ruchaud-Sparagano M. H., Kenny B.. ( 2011;). Proteasome-independent degradation of canonical NFκB complex components by the NleC protein of pathogenic Escherichia coli . J Biol Chem286:5100–5107 [CrossRef][PubMed]
    [Google Scholar]
  52. Nadler C., Baruch K., Kobi S., Mills E., Haviv G., Farago M., Alkalay I., Bartfeld S., Meyer T. F.. & other authors ( 2010;). The type III secretion effector NleE inhibits NF-kappaB activation. PLoS. Pathog6:e10000743 [CrossRef][PubMed]
    [Google Scholar]
  53. Nagamatsu K., Kuwae A., Konaka T., Nagai S., Yoshida S., Eguchi M., Watanabe M., Mimuro H., Koyasu S., Abe A.. ( 2009;). Bordetella evades the host immune system by inducing IL-10 through a type III effector, BopN. J Exp Med206:3073–3088 [CrossRef][PubMed]
    [Google Scholar]
  54. Nakayama M., Underhill D. M., Petersen T. W., Li B., Kitamura T., Takai T., Aderem A.. ( 2007;). Paired Ig-like receptors bind to bacteria and shape TLR-mediated cytokine production. J Immunol178:4250–4259[PubMed][CrossRef]
    [Google Scholar]
  55. Nanra J. S., Buitrago S. M., Crawford S., Ng J., Fink P. S., Hawkins J., Scully I. L., McNeil L. K., Aste-Amézaga J. M.. & other authors ( 2012;). Capsular polysaccharides are an important immune evasion mechanism for Staphylococcus aureus . Hum Vaccin Immunother9:[PubMed]
    [Google Scholar]
  56. Neish A. S., Gewirtz A. T., Zeng H., Young A. N., Hobert M. E., Karmali V., Rao A. S., Madara J. L.. ( 2000;). Prokaryotic regulation of epithelial responses by inhibition of IκB-α ubiquitination. Science289:1560–1563 [CrossRef][PubMed]
    [Google Scholar]
  57. Nestle F. O., Di Meglio P., Qin J. Z., Nickoloff B. J.. ( 2009;). Skin immune sentinels in health and disease. Nat Rev Immunol9:679–691[PubMed]
    [Google Scholar]
  58. Newman R. M., Salunkhe P., Godzik A., Reed J. C.. ( 2006;). Identification and characterization of a novel bacterial virulence factor that shares homology with mammalian Toll/interleukin-1 receptor family proteins. Infect Immun74:594–601 [CrossRef][PubMed]
    [Google Scholar]
  59. Newton K., Dixit V. M.. ( 2012;). Signaling in innate immunity and inflammation. Cold Spring Harb Perspect Biol4:a006049 [CrossRef][PubMed]
    [Google Scholar]
  60. Newton H. J., Pearson J. S., Badea L., Kelly M., Lucas M., Holloway G., Wagstaff K. M., Dunstone M. A., Sloan J.. & other authors ( 2010;). The type III effectors NleE and NleB from enteropathogenic E. coli and OspZ from Shigella block nuclear translocation of NF-κB p65. PLoS Pathog6:e1000898 [CrossRef][PubMed]
    [Google Scholar]
  61. Nish S., Medzhitov R.. ( 2011;). Host defense pathways: role of redundancy and compensation in infectious disease phenotypes. Immunity34:629–636 [CrossRef][PubMed]
    [Google Scholar]
  62. O’Neill L. A., Bowie A. G.. ( 2007;). The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol7:353–364 [CrossRef][PubMed]
    [Google Scholar]
  63. O’Riordan K., Lee J. C.. ( 2004;). Staphylococcus aureus capsular polysaccharides. Clin Microbiol Rev17:218–234 [CrossRef][PubMed]
    [Google Scholar]
  64. Oeckinghaus A., Hayden M. S., Ghosh S.. ( 2011;). Crosstalk in NF-κB signaling pathways. Nat Immunol12:695–708 [CrossRef][PubMed]
    [Google Scholar]
  65. Pearson J. S., Riedmaier P., Marchès O., Frankel G., Hartland E. L.. ( 2011;). A type III effector protease NleC from enteropathogenic Escherichia coli targets NF-κB for degradation. Mol Microbiol80:219–230 [CrossRef][PubMed]
    [Google Scholar]
  66. Pennini M. E., Perkins D. J., Salazar A. M., Lipsky M., Vogel S. N.. ( 2013;). Complete dependence on IRAK4 kinase activity in TLR2, but not TLR4, signaling pathways underlies decreased cytokine production and increased susceptibility to Streptococcus pneumoniae infection in IRAK4 kinase-inactive mice. J Immunol190:307–316 [CrossRef][PubMed]
    [Google Scholar]
  67. Pham T. H., Gao X., Tsai K., Olsen R., Wan F., Hardwidge P. R.. ( 2012;). Functional differences and interactions between the Escherichia coli type III secretion system effectors NleH1 and NleH2. Infect Immun80:2133–2140 [CrossRef][PubMed]
    [Google Scholar]
  68. Poltorak A., He X., Smirnova I., Liu M. Y., Van Huffel C., Du X., Birdwell D., Alejos E., Silva M.. & other authors ( 1998;). Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science282:2085–2088 [CrossRef][PubMed]
    [Google Scholar]
  69. Radhakrishnan G. K., Yu Q., Harms J. S., Splitter G. A.. ( 2009;). Brucella TIR domain-containing protein mimics properties of the Toll-like receptor adaptor protein TIRAP. J Biol Chem284:9892–9898 [CrossRef][PubMed]
    [Google Scholar]
  70. Salcedo S. P., Marchesini M. I., Lelouard H., Fugier E., Jolly G., Balor S., Muller A., Lapaque N., Demaria O.. & other authors ( 2008;). Brucella control of dendritic cell maturation is dependent on the TIR-containing protein Btp1. PLoS Pathog4:e21 [CrossRef][PubMed]
    [Google Scholar]
  71. Sanada T., Kim M., Mimuro H., Suzuki M., Ogawa M., Oyama A., Ashida H., Kobayashi T., Koyama T.. & other authors ( 2012;). The Shigella flexneri effector OspI deamidates UBC13 to dampen the inflammatory response. Nature483:623–626 [CrossRef][PubMed]
    [Google Scholar]
  72. Sengupta D., Koblansky A., Gaines J., Brown T., West A. P., Zhang D., Nishikawa T., Park S. G., Roop R. M. II, Ghosh S.. ( 2010;). Subversion of innate immune responses by Brucella through the targeted degradation of the TLR signaling adapter, MAL. J Immunol184:956–964 [CrossRef][PubMed]
    [Google Scholar]
  73. Shames S. R., Bhavsar A. P., Croxen M. A., Law R. J., Mak S. H., Deng W., Li Y., Bidshari R., de Hoog C. L.. & other authors ( 2011;). The pathogenic Escherichia coli type III secreted protease NleC degrades the host acetyltransferase p300. Cell Microbiol13:1542–1557 [CrossRef][PubMed]
    [Google Scholar]
  74. Slevogt H., Zabel S., Opitz B., Hocke A., Eitel J., N’guessan P. D., Lucka L., Riesbeck K., Zimmermann W.. & other authors ( 2008;). CEACAM1 inhibits Toll-like receptor 2-triggered antibacterial responses of human pulmonary epithelial cells. Nat Immunol9:1270–1278 [CrossRef][PubMed]
    [Google Scholar]
  75. Spear A. M., Loman N. J., Atkins H. S., Pallen M. J.. ( 2009;). Microbial TIR domains: not necessarily agents of subversion?. Trends Microbiol17:393–398 [CrossRef][PubMed]
    [Google Scholar]
  76. Spear A. M., Rana R., Jenner D. C., Flick-Smith H. C., Oyston P. C., Simpson P., Matthews S., Byrne B., Atkins H. S.. ( 2012;). A TIR domain protein from Yersinia pestis interacts with mammalian IL-1/TLR pathways but does not play a central role in the virulence of Y. pestis in a mouse model of bubonic plague. Microbiology158:1593–1606 [CrossRef][PubMed]
    [Google Scholar]
  77. Suhir H., Etzioni A.. ( 2010;). The role of Toll-like receptor signaling in human immunodeficiencies. Clin Rev Allergy Immunol38:11–19 [CrossRef][PubMed]
    [Google Scholar]
  78. Sun S. C.. ( 2012;). The noncanonical NF-κB pathway. Immunol Rev246:125–140 [CrossRef][PubMed]
    [Google Scholar]
  79. Sweet C. R., Conlon J., Golenbock D. T., Goguen J., Silverman N.. ( 2007;). YopJ targets TRAF proteins to inhibit TLR-mediated NF-κB, MAPK and IRF3 signal transduction. Cell Microbiol9:2700–2715 [CrossRef][PubMed]
    [Google Scholar]
  80. Takeda K., Akira S.. ( 2004;). TLR signaling pathways. Semin Immunol16:3–9 [CrossRef][PubMed]
    [Google Scholar]
  81. Takeuchi O., Hoshino K., Akira S.. ( 2000;). Cutting edge: TLR2-deficient and MyD88-deficient mice are highly susceptible to Staphylococcus aureus infection. J Immunol165:5392–5396[PubMed][CrossRef]
    [Google Scholar]
  82. Thurlow L. R., Thomas V. C., Fleming S. D., Hancock L. E.. ( 2009;). Enterococcus faecalis capsular polysaccharide serotypes C and D and their contributions to host innate immune evasion. Infect Immun77:5551–5557 [CrossRef][PubMed]
    [Google Scholar]
  83. Turvey S. E., Hawn T. R.. ( 2006;). Towards subtlety: understanding the role of Toll-like receptor signaling in susceptibility to human infections. Clin Immunol120:1–9 [CrossRef][PubMed]
    [Google Scholar]
  84. Underhill D. M., Ozinsky A., Hajjar A. M., Stevens A., Wilson C. B., Bassetti M., Aderem A.. ( 1999;). The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens. Nature401:811–815 [CrossRef][PubMed]
    [Google Scholar]
  85. van der Windt G. J., Blok D. C., Hoogerwerf J. J., Lammers A. J., de Vos A. F., Van’t Veer C., Florquin S., Kobayashi K. S., Flavell R. A., van der Poll T.. ( 2012;). Interleukin 1 receptor-associated kinase m impairs host defense during pneumococcal pneumonia. J Infect Dis205:1849–1857 [CrossRef][PubMed]
    [Google Scholar]
  86. Veldkamp K. E., van Strijp J. A.. ( 2009;). Innate immune evasion by staphylococci. Adv Exp Med Biol666:19–31 [CrossRef][PubMed]
    [Google Scholar]
  87. von Bernuth H., Picard C., Puel A., Casanova J. L.. ( 2012;). Experimental and natural infections in MyD88- and IRAK-4-deficient mice and humans. Eur J Immunol42:3126–3135 [CrossRef][PubMed]
    [Google Scholar]
  88. Wan F., Lenardo M. J.. ( 2010;). The nuclear signaling of NF-κB: current knowledge, new insights, and future perspectives. Cell Res20:24–33 [CrossRef][PubMed]
    [Google Scholar]
  89. Wan F., Anderson D. E., Barnitz R. A., Snow A., Bidere N., Zheng L., Hegde V., Lam L. T., Staudt L. M.. & other authors ( 2007;). Ribosomal protein S3: a KH domain subunit in NF-κB complexes that mediates selective gene regulation. Cell131:927–939 [CrossRef][PubMed]
    [Google Scholar]
  90. Wan F., Weaver A., Gao X., Bern M., Hardwidge P. R., Lenardo M. J.. ( 2011;). IKKβ phosphorylation regulates RPS3 nuclear translocation and NF-κB function during infection with Escherichia coli strain O157:H7. Nat Immunol12:335–343 [CrossRef][PubMed]
    [Google Scholar]
  91. Wanke I., Steffen H., Christ C., Krismer B., Götz F., Peschel A., Schaller M., Schittek B.. ( 2011;). Skin commensals amplify the innate immune response to pathogens by activation of distinct signaling pathways. J Invest Dermatol131:382–390 [CrossRef][PubMed]
    [Google Scholar]
  92. Watters T. M., Kenny E. F., O’Neill L. A.. ( 2007;). Structure, function and regulation of the Toll/IL-1 receptor adaptor proteins. Immunol Cell Biol85:411–419 [CrossRef][PubMed]
    [Google Scholar]
  93. Wolfert M. A., Roychowdhury A., Boons G. J.. ( 2007;). Modification of the structure of peptidoglycan is a strategy to avoid detection by nucleotide-binding oligomerization domain protein 1. Infect Immun75:706–713 [CrossRef][PubMed]
    [Google Scholar]
  94. Xavier R. J., Podolsky D. K.. ( 2000;). Microbiology. How to get along–friendly microbes in a hostile world. Science289:1483–1484 [CrossRef][PubMed]
    [Google Scholar]
  95. Xu Y., Tao X., Shen B., Horng T., Medzhitov R., Manley J. L., Tong L.. ( 2000;). Structural basis for signal transduction by the Toll/interleukin-1 receptor domains. Nature408:111–115 [CrossRef][PubMed]
    [Google Scholar]
  96. Yadav M., Zhang J., Fischer H., Huang W., Lutay N., Cirl C., Lum J., Miethke T., Svanborg C.. ( 2010;). Inhibition of TIR domain signaling by TcpC: MyD88-dependent and independent effects on Escherichia coli virulence. PLoS Pathog6:e1001120 [CrossRef][PubMed]
    [Google Scholar]
  97. Yan D., Wang X., Luo L., Cao X., Ge B.. ( 2012;). Inhibition of TLR signaling by a bacterial protein containing immunoreceptor tyrosine-based inhibitory motifs. Nat Immunol13:1063–1071 [CrossRef][PubMed]
    [Google Scholar]
  98. Ye Z., Petrof E. O., Boone D., Claud E. C., Sun J.. ( 2007;). Salmonella effector AvrA regulation of colonic epithelial cell inflammation by deubiquitination. Am J Pathol171:882–892 [CrossRef][PubMed]
    [Google Scholar]
  99. Yen H., Ooka T., Iguchi A., Hayashi T., Sugimoto N., Tobe T.. ( 2010;). NleC, a type III secretion protease, compromises NF-κB activation by targeting p65/RelA. PLoS Pathog6:e1001231 [CrossRef][PubMed]
    [Google Scholar]
  100. Yokoyama R., Itoh S., Kamoshida G., Takii T., Fujii S., Tsuji T., Onozaki K.. ( 2012;). Staphylococcal superantigen-like protein 3 binds to the Toll-like receptor 2 extracellular domain and inhibits cytokine production induced by Staphylococcus aureus, cell wall component, or lipopeptides in murine macrophages. Infect Immun80:2816–2825 [CrossRef][PubMed]
    [Google Scholar]
  101. Zhang Q., Zmasek C. M., Cai X., Godzik A.. ( 2011a;). TIR domain-containing adaptor SARM is a late addition to the ongoing microbe-host dialog. Dev Comp Immunol35:461–468 [CrossRef][PubMed]
    [Google Scholar]
  102. Zhang L., Ding X., Cui J., Xu H., Chen J., Gong Y. N., Hu L., Zhou Y., Ge J.. & other authors ( 2011b;). Cysteine methylation disrupts ubiquitin-chain sensing in NF-κB activation. Nature481:204–208 [CrossRef][PubMed]
    [Google Scholar]
  103. Zhou H., Monack D. M., Kayagaki N., Wertz I., Yin J., Wolf B., Dixit V. M.. ( 2005;). Yersinia virulence factor YopJ acts as a deubiquitinase to inhibit NF-κ B activation. J Exp Med202:1327–1332 [CrossRef][PubMed]
    [Google Scholar]
  104. Zhu J., Mohan C.. ( 2010;). Toll-like receptor signaling pathways–therapeutic opportunities. Mediators Inflamm2010:781235 [CrossRef][PubMed]
    [Google Scholar]
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