TLR-dependent human mucosal epithelial cell responses to microbial pathogens

Frontiers in Immunology

Volumn 5, Issue AUG, 2014, Pages

  McClure, Ryan ^a   Massari, Paola ^a  

^a BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Bacteria; Epithelial cells; Immunity; Mucosal tissues; Pattern recognition receptors

Indexed keywords

ADAPTOR PROTEIN; ARMADILLO DOMAIN PROTEIN; GAMMA INTERFERON; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERFERON REGULATORY FACTOR 7; INTERLEUKIN 1; INTERLEUKIN 1 RECEPTOR ASSOCIATED KINASE 1; INTERLEUKIN 1 RECEPTOR ASSOCIATED KINASE 2; INTERLEUKIN 1 RECEPTOR ASSOCIATED KINASE 4; LIPID BINDING PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE; MYELOID DIFFERENTIATION FACTOR 88; NUCLEOTIDE BINDING OLIGOMERIZATION DOMAIN PROTEIN; RECEPTOR INTERACTING PROTEIN 140; TOLL LIKE RECEPTOR; TOLL LIKE RECEPTOR ADAPTOR MOLECULE 1; TOLL LIKE RECEPTOR ADAPTOR MOLECULE 2; TRANSFORMING GROWTH FACTOR BETA ACTIVATED KINASE 1; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 6; ALPHA DEFENSIN; BETA DEFENSIN; INTERLEUKIN 1 RECEPTOR; INTERLEUKIN 5; INTERLEUKIN 6; INTERLEUKIN 8; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; PATHOGEN ASSOCIATED MOLECULAR PATTERN; RANTES; TOLL LIKE RECEPTOR 1; TOLL LIKE RECEPTOR 10; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 3; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 5; TOLL LIKE RECEPTOR 6; TOLL LIKE RECEPTOR 7; TOLL LIKE RECEPTOR 8; TOLL LIKE RECEPTOR 9; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 3;

ANTIGEN PRESENTING CELL; CELL ACTIVATION; CELLULAR IMMUNITY; CHRONIC OBSTRUCTIVE LUNG DISEASE; EPITHELIUM CELL; GENE ACTIVATION; GENE EXPRESSION; HAEMOPHILUS INFLUENZAE; HUMAN; IMMUNE RESPONSE; IMMUNOREGULATION; PATHOGENESIS; PATTERN RECOGNITION; PROTEIN EXPRESSION; PSEUDOMONAS AERUGINOSA; REVIEW; SIGNAL TRANSDUCTION; UPREGULATION; URINARY TRACT INFECTION; ADAPTIVE IMMUNITY; CROHN DISEASE; DOWN REGULATION; INNATE IMMUNITY; INTESTINE EPITHELIUM; MOUTH MUCOSA; MUCOSAL EPITHELIUM CELL; MYCOBACTERIUM TUBERCULOSIS; NEOPLASM; PORPHYROMONAS GINGIVALIS; RESPIRATORY EPITHELIUM;

EID: 84925246830     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2014.00386     Document Type: Review

References (179)

1. Sasai M, Yamamoto M. Pathogen recognition receptors: ligands and signaling pathways by toll-like receptors. Int Rev Immunol (2013) 32:116-33. doi:10.3109/08830185.2013.774391
2. Akira S, Hemmi H. Recognition of pathogen-associated molecular patterns by TLR family. Immunol Lett (2003) 85:85-95. doi:10.1016/S0165-2478(02) 00228-6
3. Cario E, Brown D, McKee M, Lynch-Devaney K, Gerken G, Podolsky DK. Commensal associated molecular patterns induce selective toll-like receptor trafficking from apical membrane to cytoplasmic compartments in polar-ized intestinal epithelium. AmJ Pathol (2002) 160:165-73. doi:10.1016/S0002-9440(10)64360-X
4. Matzinger P. Tolerance, danger, and the extended family. Annu Rev Immunol (1994) 12:991-1045. doi:10.1146/annurev.immunol.12.1.991
5. Brinkmann MM, Spooner E, Hoebe K, Beutler B, Ploegh HL, Kim YM. The interaction between the ER membrane protein UNC93B and TLR3, 7, and 9 is crucial for TLR signaling. J Cell Biol (2007) 177:265-75. doi:10.1083/jcb. 200612056
6. Ueta M, Nochi T, Jang MH, Park EJ, Igarashi O, Hino A, et al. Intracellu-larly expressed TLR2s and TLR4s contribution to an immunosilent environment at the ocular mucosal epithelium. J Immunol (2004) 173:3337-47. doi:10.4049/jimmunol.173.5.3337
7. Ioannidis I, Ye F,McNally B,Willette M, Flano E. Toll-like receptor expression and induction of type I and type III interferons in primary airway epithelial cells. J Virol (2013) 87:3261-70. doi:10.1128/JVI.01956-12
8. Medzhitov R, Preston-Hurlburt P, Kopp E, Stadlen A, Chen C, Ghosh S, et al. MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways. Mol Cell (1998) 2:253-8. doi:10.1016/S1097-2765(00)80136-7
9. Fitzgerald KA, Palsson-McDermott EM, Bowie AG, Jefferies CA, Mansell AS, Brady G, et al. Mal (MyD88-adapter-like) is required for toll-like receptor-4 signal transduction. Nature (2001) 413:78-83. doi:10.1038/35092578
10. Horng T, Barton GM, Medzhitov R. TIRAP: an adapter molecule in the toll signaling pathway. Nat Immunol (2001) 2:835-41. doi:10.1038/ni0901-835
11. Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, Sanjo H, et al. Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science (2003) 301(5633):640-3. doi:10.1126/science.1087262
12. Oshiumi H,MatsumotoM, Funami K,Akazawa T, Seya T. TICAM-1, an adap-tor molecule that participates in toll-like receptor 3-mediated interferon-beta induction. Nat Immunol (2003) 4:161-7. doi:10.1038/ni886
13. Fitzgerald KA, Rowe DC, Barnes BJ, Caffrey DR, Visintin A, Latz E, et al. LPS-TLR4 signaling to IRF-3/7 and NF-{kappa}B involves the toll adapters TRAM and TRIF. J Exp Med (2003) 198:1043-55. doi:10.1084/jem.20031023
14. Kondo T, Kawai T, Akira S. Dissecting negative regulation of toll-like receptor signaling. Trends Immunol (2012) 33:449-58. doi:10.1016/j.it.2012.05.002
15. Bell JK, Botos I, Hall PR, Askins J, Shiloach J, Davies DR, et al. The molecular structure of the TLR3 extracellular domain. J Endotoxin Res (2006) 12:375-8. doi:10.1179/096805106X118780
16. Jin MS, Kim SE, Heo JY, Lee ME, Kim HM, Paik SG, et al. Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide. Cell (2007) 130:1071-82. doi:10.1016/j.cell.2007.09.008
17. Kim HM, Park BS, Kim JI, Kim SE, Lee J, Oh SC, et al. Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist eritoran. Cell (2007) 130:906-17. doi:10.1016/j.cell.2007.08.002
18. Yoon SI, Kurnasov O, Natarajan V, Hong M, Gudkov AV, Osterman AL, et al. Structural basis of TLR5-flagellin recognition and signaling. Science (2012) 335:859-64. doi:10.1126/science.1215584
19. Tanji H, Ohto U, Shibata T, Miyake K, Shimizu T. Structural reorganization of the toll-like receptor 8 dimer induced by agonistic ligands. Science (2013) 339:1426-9. doi:10.1126/science.1229159
20. Akira S, Yamamoto M, Takeda K. Role of adapters in toll-like receptor signalling. Biochem Soc Trans (2003) 31:637-42. doi:10.1042/BST0310637
21. Gohda J, Matsumura T, Inoue J. Cutting edge: TNFR-associated factor (TRAF) 6 is essential for My D88-dependent pathway but not toll/IL-1 receptor domain-containing adaptor-inducing IFN-beta (TRIF)-dependent pathway in TLR signaling. J Immunol (2004) 173:2913-7. doi:10.4049/jimmunol.173.5. 2913
22. Meylan E, Burns K, Hofmann K, Blancheteau V,Martinon F, Kelliher M, et al. RIP1 is an essential mediator of toll-like receptor 3-induced NF-kappa B acti-vation. Nat Immunol (2004) 5:503-7. doi:10.1038/ni1061
23. Chen HC, Zhan X, Tran KK, Shen H. Selectively targeting the toll-like receptor 9 (TLR9) -IRF 7 signaling pathway by polymer blend particles. Biomaterials (2013) 34:6464-72. doi:10.1016/j.biomaterials.2013.05.016
24. Burns E, Eliyahu T, Uematsu S, Akira S, Nussbaum G. TLR2-dependent inflammatory response to Porphyromonas gingivalis is MyD88 independent, whereas My D88 is required to clear infection. J Immunol (2010) 184:1455-62. doi:10.4049/jimmunol.0900378
25. Gao Q, Qi L,Wu T,Wang J. Clostridium butyricum activates TLR2-mediated MyD88-independent signaling pathway in HT-29 cells. Mol Cell Biochem (2012) 361:31-7. doi:10.1007/s11010-011-1084-y
26. HackerH,Tseng PH,KarinM. Expanding TRAF function: TRAF3 as a tri-faced immune regulator. Nat Rev Immunol (2011) 11:457-68. doi:10.1038/nri2998
27. Tseng PH, Matsuzawa A, Zhang W, Mino T, Vignali DA, Karin M. Different modes of ubiquitination of the adaptor TRAF3 selectively activate the expression of type I interferons and proinflammatory cytokines.Nat Immunol (2010) 11:70-5. doi:10.1038/ni.1819
28. Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. Recognition of double-stranded RNA and activation of NF-kappaB by toll-like receptor 3. Nature (2001) 413:732-8. doi:10.1038/35099560
29. Kelley SL, Lukk T, Nair SK, Tapping RI. The crystal structure of human solu-ble CD14 reveals a bent solenoid with a hydrophobic amino-terminal pocket. J Immunol (2013) 190:1304-11. doi:10.4049/jimmunol.1202446
30. Song WS, Hong M, Yoon SI. Purification, crystallization and X-ray crystallo-graphic studies of ?agellin from Pseudomonas aeruginosa. Acta Crystallogr F Struct Biol Commun (2014) 70:200-2. doi:10.1107/S2053230X13034286
31. Cervantes JL, La Vake CJ, Weinerman B, Luu S, O'Connell C, Verardi PH, et al. Human TLR8 is activated upon recognition of Borrelia burgdorferi RNA in the phagosome of human monocytes. J Leukoc Biol (2013) 94:1231-41. doi:10.1189/jlb.0413206
32. Chen X, LiangH, Zhang J, Zen K, Zhang CY.microRNAs are ligands of toll-like receptors. RNA (2013) 19:737-9. doi:10.1261/rna.036319.112
33. Ohto U, Tanji H, Shimizu T. Structure and function of toll-like receptor 8. Microbes Infect (2014) 16(4):273-82. doi:10.1016/j.micinf.2014.01.007
34. Kuznik A, Bencina M, Svajger U, Jeras M, Rozman B, Jerala R. Mechanism of endosomal TLR inhibition by antimalarial drugs and imidazoquinolines. J Immunol (2011) 186:4794-804. doi:10.4049/jimmunol.1000702
35. Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, et al. A toll-like receptor recognizes bacterial DNA. Nature (2000) 408:740-5. doi:10.1038/ 35047123
36. Parroche P, Lauw FN,Goutagny N, Latz E,Monks BG,Visintin A, et al.Malaria hemozoin is immunologically inert but radically enhances innate responses by presenting malaria DNA to toll-like receptor 9. Proc Natl Acad Sci U S A (2007) 104:1919-24. doi:10.1073/pnas.0608745104
37. Regan T,Nally K,Carmody R,Houston A, Shanahan F,Macsharry J, et al. Identification of TLR10 as a key mediator of the inflammatory response to Listeria monocytogenes in intestinal epithelial cells and macrophages. J Immunol (2013) 191(12):6084-92. doi:10.4049/jimmunol.1203245
38. Lee SM, Kok KH, Jaume M, Cheung TK, Yip TF, Lai JC, et al. Toll-like receptor 10 is involved in induction of innate immune responses to influenza virus infection. Proc Natl Acad Sci USA (2014) 111:3793-8. doi:10.1073/pnas.1324266111
39. Abad C, Gonzalez-Escribano MF, Diaz-Gallo LM, Lucena-Soto JM, Mar-quez JL, Leo E, et al. Association of toll-like receptor 10 and susceptibility to Crohn's disease independent of NOD2. Genes Immun (2011) 12:635-42. doi:10.1038/gene.2011.41
40. Stevens VL, Hsing AW, Talbot JT, Zheng SL, Sun J, Chen J, et al. Genetic vari-ation in the toll-like receptor gene cluster (TLR10-TLR1-TLR6) and prostate cancer risk. Int J Cancer (2008) 123:2644-50. doi:10.1002/ijc.23826
41. Park BS,Lee JO. Recognition of lipopolysaccharide pattern by TLR4 complexes. Exp Mol Med (2013) 45:e66. doi:10.1038/emm.2013.97
42. Netea MG, van DM, Kullberg BJ, Cavaillon JM, Van der Meer JW. Does the shape of lipid A determine the interaction of LPS with toll-like receptors? Trends Immunol (2002) 23:135-9. doi:10.1016/S1471-4906(01)02169-X
43. Carpenter S,Carlson T,Dellacasagrande J,GarciaA,Gibbons S,Hertzog P, et al. TRIL, a functional component of the TLR4 signaling complex,highly expressed in brain. J Immunol (2009) 183:3989-95. doi:10.4049/jimmunol.0901518
44. Kocgozlu L, Elkaim R, Tenenbaum H, Werner S. Variable cell responses to P. gingivalis lipopolysaccharide. J Dent Res (2009) 88:741-5. doi:10.1177/ 0022034509341166
45. BiragynA,Ruffini PA,LeiferCA,Klyushnenkova E, ShakhovA,ChertovO, et al. Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2. Science (2002) 298:1025-9. doi:10.1126/science.1075565
46. Park JS, Svetkauskaite D, He Q, Kim JY, Strassheim D, Ishizaka A, et al. Involvement of toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein. J Biol Chem (2004) 279:7370-7. doi:10.1074/ jbc.M306793200
47. Peri F, Calabrese V. Toll-like receptor 4 (TLR4) modulation by synthetic and natural compounds: an update. J Med Chem (2013) 57(9):3612-22. doi:10.1021/jm401006s
48. Takeuchi O, Sato S, Horiuchi T, Hoshino K, Takeda K, Dong Z, et al. Cutting edge: role of toll-like receptor 1 in mediating immune response to microbial lipoproteins. J Immunol (2002) 169:10-4. doi:10.4049/jimmunol.169.1.10
49. Takeuchi O, Kawai T, Muhlradt PF, Morr M, Radolf JD, Zychlinsky A, et al. Discrimination of bacterial lipoproteins by toll-like receptor 6. Int Immunol (2001) 13:933-40. doi:10.1093/intimm/13.7.933
50. Buwitt-Beckmann U, Heine H, Wiesmuller KH, Jung G, Brock R, Akira S, et al. Toll-like receptor 6-independent signaling by diacylated lipopeptides. Eur J Immunol (2005) 35:282-9. doi:10.1002/eji.200424955
51. van BJ, Plantinga TS, Joosten LA, Netea MG, Folkerts G, Kraneveld AD, et al. TLR2 & Co: a critical analysis of the complex interactions between TLR2 and coreceptors. J Leukoc Biol (2013) 94:885-902. doi:10.1189/jlb.0113003
52. Ranoa DR, Kelley SL, Tapping RI. Human lipopolysaccharide-binding pro-tein (LBP) and CD14 independently deliver triacylated lipoproteins to toll-like receptor 1 (TLR1) and TLR2 and enhance formation of the ternary signaling complex. J Biol Chem (2013) 288:9729-41. doi:10.1074/jbc.M113.453266
53. Schroder NW, Morath S, Alexander C, Hamann L, Hartung T, Zahringer U, et al. Lipoteichoic acid (LTA) of S. pneumoniae and S. aureus activates immune cells via toll-like receptor (TLR)-2, LPS binding protein (LBP) and CD14 while TLR-4 and MD-2 are not involved. J Biol Chem (2003) 278(18):15587-94. doi:10.1074/jbc.M212829200
54. Tapping RI, Tobias PS. Mycobacterial lipoarabinomannan mediates physical interactions between TLR1 and TLR2 to induce signaling. J Endotoxin Res (2003) 9:264-8. doi:10.1179/096805103225001477
55. Yadav M, Schorey JS. The beta-glucan receptor dectin-1 functions together with TLR2 to mediate macrophage activation by mycobacteria. Blood (2006) 108:3168-75. doi:10.1182/blood-2006-05-024406
56. SatoM, SanoH, IwakiD,Kudo K,KonishiM,TakahashiH, et al.Direct binding of toll-like receptor 2 to zymosan, and zymosan-induced NF-kappa B activa-tion and TNF-alpha secretion are down-regulated by lung collectin surfactant protein A. J Immunol (2003) 171:417-25. doi:10.4049/jimmunol.171.1.417
57. Kang JY,Nan X, JinMS,Youn SJ, Ryu YH,Mah S, et al. Recognition of lipopep-tide patterns by toll-like receptor 2-toll-like receptor 6 heterodimer. Immunity (2009) 31:873-84. doi:10.1016/j.immuni.2009.09.018
58. Travassos LH, Girardin SE, Philpott DJ, Blanot D, Nahori MA,Werts C, et al. Toll-like receptor 2-dependent bacterial sensing does not occur via peptidogly-can recognition. EMBO Rep (2004) 5:1000-6. doi:10.1038/sj.embor.7400248
59. Williams A, Flavell RA, Eisenbarth SC. The role of NOD-like receptors in shap-ing adaptive immunity. Curr Opin Immunol (2010) 22:34-40. doi:10.1016/j. coi.2010.01.004
60. Massari P, Visintin A, Gunawardana J, Halmen KA, King CA, Golenbock DT, et al. Meningococcal porin PorB binds to TLR2 and requires TLR1 for signal-ing. J Immunol (2006) 176:2373-80. doi:10.4049/jimmunol.176.4.2373
61. Liu X, Wetzler LM, Nascimento LO, Massari P. Human airway epithelial cell responses to Neisseria lactamica and purified porin via toll-like recep-tor 2-dependent signaling. Infect Immun (2010) 78:5314-23. doi:10.1128/IAI. 00681-10
62. Toussi DN, Carraway M,Wetzler LM, Lewis LA, Liu X, Massari P. The amino acid sequence of Neisseria lactamica PorB surface-exposed loops influences toll-like receptor 2-dependent cell activation. Infect Immun (2012) 80:3417-28. doi:10.1128/IAI.00683-12
63. Toussi DN, Liu X,Massari P. The FomA porin from Fusobacterium nucleatum is a toll-like receptor 2 agonist with immune adjuvant activity. Clin Vaccine Immunol (2012) 19:1093-101. doi:10.1128/CVI.00236-12
64. Massari P, Toussi DN, Tifrea DF, de laMaza LM. Toll-like receptor 2-dependent activity of native major outer membrane protein proteosomes of Chlamydia trachomatis. Infect Immun (2013) 81:303-10. doi:10.1128/IAI.01062-12
65. Biswas A, Banerjee P, Mukherjee G, Biswas T. Porin of Shigella dysente-riae activates mouse peritoneal macrophage through toll-like receptors 2 and 6 to induce polarized type I response. Mol Immunol (2007) 44:812-20. doi:10.1016/j.molimm.2006.04.007
66. Moreno-Eutimio MA, Tenorio-Calvo A, Pastelin-Palacios R, Perez-Shibayama C, Gil-Cruz C, Lopez-Santiago R, et al. Salmonella typhi OmpS1 and OmpS2 porins are potent protective immunogens with adjuvant properties. Immunology (2013) 139:459-71. doi:10.1111/imm.12093
67. Galdiero M, Galdiero M, Finamore E, Rossano F, Gambuzza M, Catania MR, et al. Haemophilus influenzae porin induces toll-like receptor 2-mediated cytokine production in human monocytes and mouse macrophages. Infect Immun (2004) 72:1204-9. doi:10.1128/IAI.72.2.1204-1209.2004
68. Cody V, Pace J,Nawar HF, King-Lyons N, Liang S, Connell TD, et al. Structure-activity correlations of variant forms of the B pentamer of Escherichia coli type II heat-labile enterotoxin LT-IIb with toll-like receptor 2 bind-ing. Acta Crystallogr D Biol Crystallogr (2012) 68:1604-12. doi:10.1107/ S0907444912038917
69. Davey M, Liu X, Ukai T, Jain V, Gudino C, Gibson FC III, et al. Bacterial fim-briae stimulate proinflammatory activation in the endothelium through dis-tinct TLRs. J Immunol (2008) 180:2187-95. doi:10.4049/jimmunol.180.4.2187
70. Nair S, Ramaswamy PA, Ghosh S, Joshi DC, Pathak N, Siddiqui I, et al. The PPE18 of Mycobacterium tuberculosis interacts with TLR2 and activates IL-10 induction in macrophage. J Immunol (2009) 183:6269-81. doi:10.4049/ jimmunol.0901367
71. Beklen A, Hukkanen M, Richardson R, Konttinen YT. Immuno histochemical localization of toll-like receptors 1-10 in periodontitis.OralMicrobiol Immunol (2008) 23:425-31. doi:10.1111/j.1399-302X.2008.00448.x
72. SemlaliA,Witoled C,AlanaziM,RouabhiaM.Whole cigarette smoke increased the expression of TLRs, HBDs, and proinflammory cytokines by human gin-gival epithelial cells through different signaling pathways. PLoS One (2012) 7:e52614. doi:10.1371/journal.pone.0052614
73. Uehara A, Fujimoto Y, Fukase K, Takada H. Various human epithelial cells express functional toll-like receptors, NOD1 and NOD2 to produce anti-microbial peptides, but not proinflammatory cytokines. Mol Immunol (2007) 44:3100-11. doi:10.1016/j.molimm.2007.02.007
74. Siponen M, Kauppila JH, Soini Y, Salo T. TLR4 and TLR9 are induced in oral lichen planus. J Oral Pathol Med (2012) 41:741-7. doi:10.1111/j.1600-0714. 2012.01169.x
75. Janardhanam SB, Prakasam S, Swaminathan VT, Kodumudi KN, Zunt SL, Srinivasan M. Differential expression of TLR-2 and TLR-4 in the epithelial cells in oral lichen planus. Arch Oral Biol (2012) 57:495-502. doi:10.1016/j. archoralbio.2011.10.013
76. Promsudthi A, Poomsawat S, LimsricharoenW. The role of toll-like receptor 2 and 4 in gingival tissues of chronic periodontitis subjects with type 2 diabetes. J Periodontal Res (2013) 49(3):346-54. doi:10.1111/jre.12112
77. Beklen A, Sorsa T, Konttinen YT. Toll-like receptors 2 and 5 in human gingival epithelial cells co-operate with T-cell cytokine interleukin-17. Oral Microbiol Immunol (2009) 24:38-42. doi:10.1111/j.1399-302X.2008.00473.x
78. Takai T, Chen X, Xie Y, Vu AT, Le TA, Kinoshita H, et al. TSLP expression induced via toll-like receptor pathways in human keratinocytes.Methods Enzy-mol (2014) 535:371-87. doi:10.1016/B978-0-12-397925-4.00021-3
79. KimY, JoAR, JangDH,ChoYJ,Chun J,Min BM, et al. Toll-like receptor 9medi-ates oral bacteria-induced IL-8 expression in gingival epithelial cells. Immunol Cell Biol (2012) 90:655-63. doi:10.1038/icb.2011.85
80. ManoussakisMN, SpachidouMP,Maratheftis CI. Salivary epithelial cells from Sjogren's syndrome patients are highly sensitive to anoikis induced by TLR-3 ligation. J Autoimmun (2010) 35:212-8. doi:10.1016/j.jaut.2010.06.010
81. Nishimura M, Naito S. Tissue-specific mRNA expression pro?les of human toll-like receptors and related genes. Biol Pharm Bull (2005) 28:886-92. doi:10.1248/bpb.28.886
82. LangeMJ,Lasiter JC,MisfeldtML. Toll-like receptors in tonsillar epithelial cells. Int J Pediatr Otorhinolaryngol (2009) 73:613-21. doi:10.1016/j.ijporl.2008.12. 013
83. Lim DJ, Moon SK. Establishment of cell lines from the human middle and inner ear epithelial cells. Adv Exp Med Biol (2011) 720:15-25. doi:10.1007/ 978-1-4614-0254-1_2
84. Lee HY, Takeshita T, Shimada J, Akopyan A,Woo JI, Pan H, et al. Induction of beta defensin 2 by NTHi requires TLR2 mediated MyD88 and IRAK-TRAF6-p38MAPK signaling pathway in human middle ear epithelial cells. BMC Infect Dis (2008) 8:87. doi:10.1186/1471-2334-8-87
85. SzczepanskiM,SzyfterW, JenekR,WrobelM,Lisewska IM,Zeromski J.Toll-like receptors 2, 3 and 4 (TLR-2, TLR-3 and TLR-4) are expressed in the microenvironment of human acquired cholesteatoma. Eur Arch Otorhinolaryngol (2006) 263:603-7. doi:10.1007/s00405-006-0030-1
86. Tanigawa T, Odkhuu E, Morikawa A, Hayashi K, Sato T, Shibata R, et al. Immunological role of prostaglandin E2 production inmouse auditory cells in response to LPS. Innate Immun (2013). doi:10.1177/1753425913503578
87. Redfern RL, Reins RY,McDermott AM. Toll-like receptor activationmodulates antimicrobial peptide expression by ocular surface cells. Exp Eye Res (2011) 92:209-20. doi:10.1016/j.exer.2010.12.005
88. Erdinest N, Aviel G, Moallem E, Anteby I, Yahalom C, Mechoulam H, et al. Expression and activation of toll-like receptor 3 and toll-like receptor 4 on human corneal epithelial and conjunctival ?broblasts. J Inflamm(Lond) (2014) 11:3. doi:10.1186/1476-9255-11-3
89. EbiharaN,Yamagami S,Chen L,Tokura T, IwatsuM,UshioH, et al. Expression and function of toll-like receptor-3 and -9 in human corneal myo?broblasts. Invest Ophthalmol Vis Sci (2007) 48:3069-76. doi:10.1167/iovs.06-0968
90. Kumar A, Zhang J, Yu FS. Toll-like receptor 2-mediated expression of beta-defensin-2 in human corneal epithelial cells. Microbes Infect (2006) 8:380-9. doi:10.1016/j.micinf.2005.07.006
91. Du JW, Zhang F, Capo-Aponte JE, Tachado SD, Zhang J, Yu FS, et al. AsialoGM1-mediated IL-8 release by human corneal epithelial cells requires coexpression of TLR5. Invest Ophthalmol Vis Sci (2006) 47:4810-8. doi:10. 1167/iovs.06-0250
92. Ma P,Wang Z, Pflugfelder SC, Li DQ. Toll-like receptors mediate induction of peptidoglycan recognition proteins in human corneal epithelial cells. Exp Eye Res (2010) 90:130-6. doi:10.1016/j.exer.2009.09.021
93. Pearlman E, Sun Y, Roy S, KarmakarM, Hise AG, Szczotka-Flynn L, et al. Host defense at the ocular surface. Int Rev Immunol (2013) 32:4-18. doi:10.3109/ 08830185.2012.749400
94. Zhang J,Xu K,Ambati B,Yu FS. Toll-like receptor 5-mediated corneal epithelial inflammatory responses to Pseudomonas aeruginosa ?agellin. Invest Ophthal-mol Vis Sci (2003) 44:4247-54. doi:10.1167/iovs.03-0219
95. Evans DJ, Fleiszig SM.Why does the healthy cornea resist Pseudomonas aerug-inosa infection? Am J Ophthalmol (2013) 155:961-70. doi:10.1016/j.ajo.2013. 03.001
96. Zhao J, Wu XY. Aspergillus fumigatus antigens activate immortalized human corneal epithelial cells via toll-like receptors 2 and 4. Curr Eye Res (2008) 33:447-54. doi:10.1080/02713680802130339
97. Zhang J, Kumar A, Wheater M, Yu FS. Lack of MD-2 expression in human corneal epithelial cells is an underlyingmechanismof lipopolysaccharide (LPS) unresponsiveness. Immunol Cell Biol (2009) 87:141-8. doi:10.1038/icb.2008.75
98. Brito BE, Zamora DO, Bonnah RA, Pan Y, Planck SR, Rosenbaum JT. Toll-like receptor 4 andCD14 expression in human ciliary body andTLR-4 in human iris endothelial cells. Exp Eye Res (2004) 79:203-8. doi:10.1016/j.exer.2004.03.012
99. Micera A, Stampachiacchiere B, Normando EM, Lambiase A, Bonini S, Bonini S.Nerve growth factormodulates toll-like receptor (TLR) 4 and 9 expression in cultured primaryVKC conjunctival epithelial cells.MolVis (2009) 15:2037-44.
100. Kumar MV, Nagineni CN, Chin MS, Hooks JJ, Detrick B. Innate immunity in the retina: toll-like receptor (TLR) signaling in human retinal pigment epithelial cells. JNeuroimmunol (2004) 153:7-15. doi:10.1016/j.jneuroim.2004. 04.018
101. Dong Z, Yang Z, Wang C. Expression of TLR2 and TLR4 messenger RNA in the epithelial cells of the nasal airway. Am J Rhinol (2005) 19(3):236-9.
102. Ohkuni T, Kojima T, Ogasawara N,Masaki T, Fuchimoto J, Kamekura R, et al. Poly(I:C) reduces expression of JAM-A and induces secretion of IL-8 and TNF-alpha via distinct NF-kappaB pathways in human nasal epithelial cells. Toxicol Appl Pharmacol (2011) 250:29-38. doi:10.1016/j.taap.2010.09.023
103. Ryu JH, Yoo JY, Kim MJ, Hwang SG, Ahn KC, Ryu JC, et al. Distinct TLR-mediated pathways regulate house dust mite-induced allergic disease in the upper and lower airways. J Allergy Clin Immunol (2013) 131:549-61. doi:10.1016/j.jaci.2012.07.050
104. Sha Q, Truong-Tran AQ, Plitt JR, Beck LA, Schleimer RP. Activation of airway epithelial cells by toll-like receptor agonists. Am J Respir Cell Mol Biol (2004) 31:358-64. doi:10.1165/rcmb.2003-0388OC
105. Wang X, Zhang Z, Louboutin JP, Moser C, Weiner DJ, Wilson JM. Airway epithelia regulate expression of human beta-defensin 2 through toll-like recep-tor 2. FASEB J (2003) 17(12):1727-9. doi:10.1096/fj.02-0616fje
106. Jia HP, Kline JN, Penisten A, Apicella MA, Gioannini TL,Weiss J, et al. Endo-toxin responsiveness of human airway epithelia is limited by low expres-sion of MD-2. Am J Physiol Lung Cell Mol Physiol (2004) 287:L428-37. doi:10.1152/ajplung.00377.2003
107. Berube J, Bourdon C, Yao Y, Rousseau S. Distinct intracellular signaling path-ways control the synthesis of IL-8 and RANTES in TLR1/TLR2, TLR3 or NOD1 activated human airway epithelial cells. Cell Signal (2009) 21:448-56. doi:10.1016/j.cellsig.2008.12.001
108. Zhang Z, Louboutin JP, Weiner DJ, Goldberg JB, Wilson JM. Human air-way epithelial cells sense Pseudomonas aeruginosa infection via recogni-tion of ?agellin by toll-like receptor 5. Infect Immun (2005) 73:7151-60. doi:10.1128/IAI.73.11.7151-7160.2005
109. Armstrong L, Medford AR, Uppington KM, Robertson J, Witherden IR, Tet-ley TD, et al. Expression of functional toll-like receptor-2 and -4 on alveolar epithelial cells. Am J Respir Cell Mol Biol (2004) 31:241-5. doi:10.1165/rcmb. 2004-0078OC
110. Regueiro V, Moranta D, Campos MA, Margareto J, Garmendia J, Ben-goechea JA. Klebsiella pneumoniae increases the levels of toll-like receptors 2 and 4 in human airway epithelial cells. Infect Immun (2009) 77:714-24. doi:10.1128/IAI.00852-08
111. MacRedmond RE, Greene CM, Dorscheid DR, McElvaney NG, O'Neill SJ. Epithelial expression of TLR4 is modulated in COPD and by steroids, salme-terol and cigarette smoke. Respir Res (2007) 8:84. doi:10.1186/1465-9921-8-84
112. Guillot L, Medjane S, Le Barillec K, Balloy V, Danel C, Chignard M, et al. Response of human pulmonary epithelial cells to lipopolysaccharide involves toll-like receptor 4 (TLR4)-dependent signaling pathways: evidence for an intracellular compartmentalization of TLR4. J Biol Chem (2004) 279:2712-8. doi:10.1074/jbc.M305790200
113. Lim DM, Narasimhan S, Michaylira CZ, Wang ML. TLR3-mediated NF-{kappa}B signaling in human esophageal epithelial cells. Am J Physiol Gas-trointest Liver Physiol (2009) 297:G1172-80. doi:10.1152/ajpgi.00065.2009
114. Verbeek RE, Siersema PD, Ten Kate FJ, Fluiter K, Souza RF, Vleggaar FP, et al. Toll-like receptor 4 activation in Barrett's esophagus results in a strong increase in COX-2 expression. J Gastroenterol (2013). doi:10.1007/s00535-013-0862-6
115. Pimentel-Nunes P, Afonso L, Lopes P, Roncon-Albuquerque R Jr., Goncalves N, Henrique R, et al. Increased expression of toll-like receptors (TLR) 2, 4 and 5 in gastric dysplasia. Pathol Oncol Res (2011) 17:677-83. doi:10.1007/s12253-011-9368-9
116. Pimentel-Nunes P, Goncalves N, Boal-Carvalho I, Afonso L, Lopes P, Roncon-Albuquerque R Jr., et al. Helicobacter pylori induces increased expression of toll-like receptors and decreased toll-interacting protein in gastric mucosa that persists throughout gastric carcinogenesis. Helicobacter (2013) 18:22-32. doi:10.1111/hel.12008
117. Takenaka R,Yokota K,Ayada K,MizunoM,ZhaoY, FujinamiY, et al.Helicobac-ter pylori heat-shock protein 60 induces inflammatory responses through the toll-like receptor-triggered pathway in cultured human gastric epithelial cells. Microbiology (2004) 150:3913-22. doi:10.1099/mic.0.27527-0
118. Naik S, Kelly EJ, Meijer L, Pettersson S, Sanderson IR. Absence of toll-like receptor 4 explains endotoxin hyporesponsiveness in human intestinal epithe-lium. J Pediatr Gastroenterol Nutr (2001) 32:449-53. doi:10.1097/00005176-200104000-00011
119. Eaves-Pyles T, Bu HF,Tan XD,Cong Y, Patel J,Davey RA, et al. Luminal-applied flagellin is internalized by polarized intestinal epithelial cells and elicits immune responses via the TLR5 dependent mechanism. PLoS One (2011) 6:e24869. doi:10.1371/journal.pone.0024869
120. Vamadevan AS, Fukata M, Arnold ET, Thomas LS, Hsu D, Abreu MT. Reg-ulation of toll-like receptor 4-associated MD-2 in intestinal epithelial cells: a comprehensive analysis. Innate Immun (2010) 16:93-103. doi:10.1177/ 1753425909339231
121. Biswas A, Wilmanski J, Forsman H, Hrncir T, Hao L, Tlaskalova-Hogenova H, et al. Negative regulation of toll-like receptor signaling plays an essen-tial role in homeostasis of the intestine. Eur J Immunol (2011) 41:182-94. doi:10.1002/eji.201040479
122. Hornef MW, Frisan T, Vandewalle A, Normark S, Richter-Dahlfors A. Toll-like receptor 4 resides in the Golgi apparatus and colocalizes with internalized lipopolysaccharide in intestinal epithelial cells. J Exp Med (2002) 195:559-70. doi:10.1084/jem.20011788
123. Lee J,Mo JH, Katakura K, Alkalay I, Rucker AN, Liu YT, et al. Maintenance of colonic homeostasis by distinctive apical TLR9 signalling in intestinal epithelial cells. Nat Cell Biol (2006) 8:1327-36. doi:10.1038/ncb1500
124. Menendez A,Willing BP, Montero M,Wlodarska M, So CC, Bhinder G, et al. Bacterial stimulation of the TLR-MyD88 pathway modulates the homeostatic expression of ileal Paneth cell alpha-defensins. J Innate Immun (2013) 5:39-49. doi:10.1159/000341630
125. Pudney J, Anderson DJ. Expression of toll-like receptors in genital tract tissues from normal and HIV-infected men. Am J Reprod Immunol (2011) 65:28-43. doi:10.1111/j.1600-0897.2010.00877.x
126. Mackern-Oberti JP,Motrich RD, Breser ML, Sanchez LR, Cuffini C, RiveroVE. Chlamydia trachomatis infection of the male genital tract: an update. J Reprod Immunol (2013) 100:37-53. doi:10.1016/j.jri.2013.05.002
127. Sellami H, Said-Sadier N, Znazen A, Gdoura R, Ojcius DM, Hammami A. Chlamydia trachomatis infection increases the expression of inflammatory tumorigenic cytokines and chemokines as well as components of the toll-like receptor and NF-kappaB pathways in human prostate epithelial cells. Mol Cell Probes (2014) 28(4):147-54. doi:10.1016/j.mcp.2014.01.006
128. Mackern-Oberti JP, Maccioni M, Cuffini C, Gatti G, Rivero VE. Susceptibil-ity of prostate epithelial cells to Chlamydia muridarum infection and their role in innate immunity by recruitment of intracellular toll-like receptors 4 and 2 and MyD88 to the inclusion. Infect Immun (2006) 74:6973-81. doi:10.1128/IAI.00593-06
129. PivarcsiA,Nagy I,KoreckA,KisK,Kenderessy-SzaboA, SzellM, et al.Microbial compounds induce the expression of pro-inflammatory cytokines, chemokines and human beta-defensin-2 in vaginal epithelial cells. Microbes Infect (2005) 7:1117-27. doi:10.1016/j.micinf.2005.03.016
130. Fazeli A, Bruce C, Anumba DO. Characterization of toll-like receptors in the female reproductive tract in humans. Hum Reprod (2005) 20:1372-8. doi:10.1093/humrep/deh775
131. Joseph T, Zalenskaya IA, Yousefieh N, Schriver SD, Cote LC, Chandra N, et al. Induction of cyclooxygenase (COX)-2 in human vaginal epithelial cells in response to TLR ligands and TNF-alpha. Am J Reprod Immunol (2012) 67:482-90. doi:10.1111/j.1600-0897.2011.01099.x
132. Sathe A, Reddy KV. TLR9 and RIG-I signaling in human endocervical epithe-lial cellsmodulates inflammatory responses ofmacrophages and dendritic cells in vitro. PLoS One (2014) 9:e83882. doi:10.1371/journal.pone.0083882
133. Hart KM, Murphy AJ, Barrett KT, Wira CR, Guyre PM, Pioli PA. Functional expression of pattern recognition receptors in tissues of the human female reproductive tract. J Reprod Immunol (2009) 80:33-40. doi:10.1016/j.jri.2008. 12.004
134. Schaefer TM, Fahey JV, Wright JA, Wira CR. Innate immunity in the human female reproductive tract: antiviral response of uterine epithelial cells to the TLR3 agonist poly(I:C). J Immunol (2005) 174:992-1002. doi:10.4049/ jimmunol.174.2.992
135. Yin X, Hou T, Liu Y, Chen J, Yao Z, Ma C, et al. Association of toll-like recep-tor 4 gene polymorphism and expression with urinary tract infection types in adults. PLoS One (2010) 5:e14223. doi:10.1371/journal.pone.0014223
136. NeteaMG,Wijmenga C,O'Neill LA.Genetic variation in toll-like receptors and disease susceptibility. Nat Immunol (2012) 13:535-42. doi:10.1038/ni.2284
137. Song J, Abraham SN. TLR-mediated immune responses in the urinary tract. Curr Opin Microbiol (2008) 11:66-73. doi:10.1016/j.mib.2007.12.001
138. Backhed F,Meijer L, Normark S, Richter-Dahlfors A. TLR4-dependent recog-nition of lipopolysaccharide by epithelial cells requires sCD14. Cell Microbiol (2002) 4:493-501. doi:10.1046/j.1462-5822.2002.00208.x
139. Miyazaki J, Kawai K,Oikawa T, Johraku A,Hattori K, Shimazui T, et al. Uroep-ithelial cells can directly respond to Mycobacterium bovis bacillus Calmette-Guerin through toll-like receptor signalling. BJU Int (2006) 97:860-4. doi:10. 1111/j.1464-410X.2006.06026.x
140. Zhang D, Zhang G, Hayden MS, Greenblatt MB, Bussey C, Flavell RA, et al. A toll-like receptor that prevents infection by uropathogenic bacteria. Science (2004) 303:1522-6. doi:10.1126/science.1094351
141. Svanborg C,Godaly G,HedlundM. Cytokine responses duringmucosal infections: role in disease pathogenesis and host defence.CurrOpinMicrobiol (1999) 2:99-105. doi:10.1016/S1369-5274(99)80017-4
142. McNamara PS, Fonceca AM, Howarth D, Correia JB, Slupsky JR, Trinick RE, et al. Respiratory syncytial virus infection of airway epithelial cells, in vivo and in vitro, supports pulmonary antibody responses by inducing expres-sion of the B cell differentiation factor BAFF. Thorax (2013) 68:76-81. doi:10.1136/thoraxjnl-2012-202288
143. Woo SJ, Im J, Jeon JH, Kang SS, Lee MH, Yun CH, et al. Induction of BAFF expression by IFN-gamma via JAK/STAT signaling pathways in human intesti-nal epithelial cells. J Leukoc Biol (2013) 93:363-8. doi:10.1189/jlb.0412210
144. Scott DA, Krauss J. Neutrophils in periodontal inflammation. Front Oral Biol (2012) 15:56-83. doi:10.1159/000329672
145. Liu J,Chen J,Du X,Hu L,Chen L. The expression of hBDs in the gingival tissue and keratinocytes from healthy subjects and periodontitis patients. Arch Oral Biol (2014) 59:193-8. doi:10.1016/j.archoralbio.2013.11.007
146. Lu Q, Darveau RP, Samaranayake LP,Wang CY, Jin L. Differential modulation of human {beta}-defensins expression in human gingival epithelia by Porphy-romonas gingivalis lipopolysaccharide with tetra-and penta-acylated lipid A structures. Innate Immun (2009) 15:325-35. doi:10.1177/1753425909104899
147. Hazlett L, Wu M. Defensins in innate immunity. Cell Tissue Res (2011) 343:175-88. doi:10.1007/s00441-010-1022-4
148. ChungWO,Dale BA.Differential utilization of nuclear factor-kappaB signaling pathways for gingival epithelial cell responses to oral commensal and patho-genic bacteria. OralMicrobiol Immunol (2008) 23:119-26. doi:10.1111/j.1399-302X.2007.00398.x
149. Uehara A, Sugawara S, Takada H. Priming of human oral epithelial cells by interferon-gamma to secrete cytokines in response to lipopolysaccharides, lipoteichoic acids and peptidoglycans. J Med Microbiol (2002) 51:626-34.
150. Mohammed I, Suleman H, Otri AM, Kulkarni BB, Chen P, Hopkinson A, et al. Localization and gene expression of human beta-defensin 9 at the human ocular surface epithelium. InvestOphthalmolVis Sci (2010) 51:4677-82. doi:10.1167/iovs.10-5334
151. Otri AM, Mohammed I, Al-Aqaba MA, Fares U, Peng C, Hopkinson A, et al. Variable expression of human beta defensins 3 and 9 at the human ocular surface in infectious keratitis. Invest Ophthalmol Vis Sci (2012) 53:757-61. doi:10.1167/iovs.11-8467
152. Zhang L, Che C, Lin J, Liu K, Li DQ, Zhao G. TLR-mediated induction of proinflammatory cytokine IL-32 in corneal epithelium. Curr Eye Res (2013) 38:630-8. doi:10.3109/02713683.2012.763102
153. Ohnishi T,Muroi M, Tanamoto K. The lipopolysaccharide-recognition mech-anism in cells expressing TLR4 and CD14 but lacking MD-2. FEMS Immunol Med Microbiol (2007) 51:84-91. doi:10.1111/j.1574-695X.2007.00281.x
154. Frank DN, Feazel LM, Bessesen MT, Price CS, Janoff EN, Pace NR. The human nasal microbiota and Staphylococcus aureus carriage. PLoS One (2010) 5:e10598. doi:10.1371/journal.pone.0010598
155. BautistaMV,Chen Y, IvanovaVS, RahimiMK,Watson AM, RoseMC. IL-8 reg-ulates mucin gene expression at the posttranscriptional level in lung epithelial cells. J Immunol (2009) 183:2159-66. doi:10.4049/jimmunol.0803022
156. Ueno K, Koga T, Kato K,Golenbock DT,Gendler SJ, Kai H, et al.MUC1mucin is a negative regulator of toll-like receptor signaling. Am J Respir Cell Mol Biol (2008) 38:263-8. doi:10.1165/rcmb.2007-0336RC
157. Alekseeva L, Huet D, Femenia F, Mouyna I, Abdelouahab M, Cagna A, et al. Inducible expression of beta defensins by human respiratory epithelial cells exposed to Aspergillus fumigatus organisms. BMC Microbiol (2009) 9:33. doi:10.1186/1471-2180-9-33
158. Bals R,Wang X, Zasloff M,Wilson JM. The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface. Proc Natl Acad Sci U S A (1998) 95:9541-6. doi:10.1073/pnas.95.16.9541
159. Wu CA, Peluso JJ, Zhu L, Lingenheld EG,Walker ST, Puddington L. Bronchial epithelial cells produce IL-5: implications for local immune responses in the airways. Cell Immunol (2010) 264:32-41. doi:10.1016/j.cellimm.2010.04.008
160. Levy DE, Marie IJ, Durbin JE. Induction and function of type I and III interferon in response to viral infection. Curr Opin Virol (2011) 1:476-86. doi:10.1016/j.coviro.2011.11.001
161. Kato A, Truong-Tran AQ, Scott AL, Matsumoto K, Schleimer RP. Airway epithelial cells produce B cell-activating factor of TNF family by an IFN-beta-dependent mechanism. J Immunol (2006) 177:7164-72. doi:10.4049/ jimmunol.177.10.7164
162. Wald D, Qin J, Zhao Z, Qian Y, Naramura M, Tian L, et al. SIGIRR, a negative regulator of toll-like receptor-interleukin 1 receptor signaling. Nat Immunol (2003) 4:920-7. doi:10.1038/ni968
163. Ostaff MJ, Stange EF, Wehkamp J. Antimicrobial peptides and gut micro-biota in homeostasis and pathology. EMBO Mol Med (2013) 5:1465-83. doi:10.1002/emmm.201201773
164. Bahrami B,Macfarlane S,Macfarlane GT. Induction of cytokine formation by human intestinal bacteria in gut epithelial cell lines. J Appl Microbiol (2011) 110:353-63. doi:10.1111/j.1365-2672.2010.04889.x
165. Wells JM, Rossi O,MeijerinkM, van BP. Epithelial crosstalk at the microbiota-mucosal interface. Proc Natl Acad Sci U S A (2011) 108(Suppl 1):4607-14. doi:10.1073/pnas.1000092107
166. Jarry A, Bossard C, Bou-Hanna C, Masson D, Espaze E, Denis MG, et al. Mucosal IL-10 and TGF-beta play crucial roles in preventing LPS-driven, IFN-gamma-mediated epithelial damage in human colon explants. J Clin Invest (2008) 118:1132-42. doi:10.1172/JCI32140
167. Mach J, Hshieh T, Hsieh D, Grubbs N, Chervonsky A. Development of intesti-nal M cells. Immunol Rev (2005) 206:177-89. doi:10.1111/j.0105-2896.2005. 00281.x
168. Mora JR, Iwata M, Eksteen B, Song SY, Junt T, Senman B, et al. Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells. Science (2006) 314:1157-60. doi:10.1126/science.1132742
169. Palladino MA, Johnson TA, Gupta R, Chapman JL, Ojha P. Members of the toll-like receptor family of innate immunity pattern-recognition receptors are abundant in the male rat reproductive tract. Biol Reprod (2007) 76:958-64. doi:10.1095/biolreprod.106.059410
170. Fraczek M, Kurpisz M. Inflammatory mediators exert toxic effects of oxidative stress on human spermatozoa. J Androl (2007) 28:325-33. doi:10.2164/jandrol. 106.001149
171. Fichorova RN, Cronin AO, Lien E, Anderson DJ, Ingalls RR. Response to Neisseria gonorrhoeae by cervicovaginal epithelial cells occurs in the absence of toll-like receptor 4-mediated signaling. J Immunol (2002) 168:2424-32. doi:10.4049/jimmunol.168.5.2424
172. Yenugu S, Hamil KG, Birse CE, Ruben SM, French FS, Hall SH. Antibacterial properties of the sperm-binding proteins and peptides of human epididymis 2 (HE2) family; salt sensitivity, structural dependence and their interaction with outer and cytoplasmic membranes of Escherichia coli. Biochem J (2003) 372:473-83. doi:10.1042/BJ20030225
173. Com E, Bourgeon F, Evrard B, Ganz T, Colleu D, Jegou B, et al. Expression of antimicrobial defensins in the male reproductive tract of rats, mice, and humans. Biol Reprod (2003) 68:95-104. doi:10.1095/biolreprod.102.005389
174. Fichorova RN, Desai PJ, Gibson FC III, Genco CA. Distinct proinflam-matory host responses to Neisseria gonorrhoeae infection in immortalized human cervical and vaginal epithelial cells. Infect Immun (2001) 69:5840-8. doi:10.1128/IAI.69.9.5840-5848.2001
175. AgrawalT,VatsV, Salhan S,MittalA.Themucosal immune response toChlamy-dia trachomatis infection of the reproductive tract inwomen. J Reprod Immunol (2009) 83:173-8. doi:10.1016/j.jri.2009.07.013
176. Wallace PK, Yeaman GR, Johnson K,Collins JE, Guyre PM, Wira CR. MHCclass II expression and antigen presentation by human endometrial cells. J Steroid Biochem Mol Biol (2001) 76:203-11. doi:10.1016/S0960-0760(00)00149-7
177. Al-MouslyN,EleyA. Interaction of Chlamydia trachomatis serovar Ewithmale genital tract epithelium results in secretion of proinflammatory cytokines. J Med Microbiol (2007) 56:1025-32. doi:10.1099/jmm.0.47241-0
178. Dixit E, Kagan JC. Intracellular pathogen detection by RIG-I-like receptors. Adv Immunol (2013) 117:99-125. doi:10.1016/B978-0-12-410524-9.00004-9
179. Rahman AH, Eisenberg RA. The role of toll-like receptors in systemic lupus erythematosus. Springer Semin Immunopathol (2006) 28:131-43. doi:10.1007/ s00281-006-0034-3