Th17 responses and host defense against microorganisms: an overview

  • Van De Veerdonk, Frank L. ;
  • Gresnigt, Mark S. ;
  • Kullberg, Bart Jan ;
  • Van Der Meer, Jos W.M. ;
  • Joosten, Leo A.B. ;
  • Netea, Mihai G.
  • Published : 2009.12.31


T helper (Th) 17 cells have recently been described as a third subset of T helper cells, and have provided new insights into the mechanisms that are important in the development of autoimmune diseases and the immune responses that are essential for effective antimicrobial host defense. Both protective and harmful effects of Th17 responses during infection have been described. In general, Th17 responses are critical for mucosal and epithelial host defense against extracellular bacteria and fungi. However, recent studies have reported that Th17 responses can also contribute to viral persistence and chronic inflammation associated with parasitic infection. It has become evident that the type of microorganisms and the setting in which they trigger the Th17 response determines the outcome of the delicate balancethat exists between Th17 induced protection and immunopathogenesis.


Chronic inflammation;Cytokine;T helper cell;Th 17 immune response;Viral infection


  1. Bozza, S., Zelante, T., Moretti, S., Bonifazi, P., DeLuca, A., D'Angelo, C., Giovannini, G., Garlanda, C., Boon, L., Bistoni, F., Puccetti, P., Mantovani, A. and Romani, L. (2008) Lack of Toll IL-1R8 exacerbates Th17 cell responses in fungal infection. J. Immunol. 180, 4022-4031
  2. Romani, L., Fallarino, F., De Luca, A., Montagnoli, C., D'Angelo, C., Zelante, T., Vacca, C., Bistoni, F., Fioretti, M. C., Grohmann, U., Segal, B. H. and Puccetti, P. (2008) Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease. Nature 451, 211-215
  3. Luzza, F., Parrello, T., Monteleone, G., Sebkova, L., Romano, M., Zarrilli, R., Imeneo, M. and Pallone, F. (2000) Up-regulation of IL-17 is associated with bioactive IL-8 expression in Helicobacter pylori-infected human gastric mucosa. J. Immunol. 165, 5332-5337
  4. Mangan, P. R., Harrington, L. E., O'Quinn, D. B., Helms, W. S., Bullard, D. C., Elson, C. O., Hatton, R. D., Wahl, S. M., Schoeb, T. R. and Weaver, C. T. (2006) Transforming growth factor-beta induces development of the T(H)17 lineage. Nature 441, 231-234
  5. Glaser, J. B., Morton-Kute, L., Berger, S. R., Weber, J., Siegal, F. P., Lopez, C., Robbins, W. and Landesman, S. H. (1985) Recurrent Salmonella typhimurium bacteremia associated with the acquired immunodeficiency syndrome. Ann. Intern. Med. 102, 189-193
  6. Khader, S. A. and Cooper, A. M. (2008) IL-23 and IL-17 in tuberculosis. Cytokine. 41, 79-83
  7. Higgins, S. C., Jarnicki, A. G., Lavelle, E. C. and Mills, K. H. (2006) TLR4 mediates vaccine-induced protective cellular immunity to Bordetella pertussis: role of IL-17-producing T cells. J. Immunol. 177, 7980-7989
  8. Andreasen, C., Powell, D. A. and Carbonetti, N. H. (2009) Pertussis toxin stimulates IL-17 production in response to Bordetella pertussis infection in mice. PLoS One 4, e7079
  9. Siciliano, N. A., Skinner, J. A. and Yuk, M. H. (2006) Bordetella bronchiseptica modulates macrophage phenotype leading to the inhibition of CD4+ T cell proliferation and the initiation of a Th17 immune response. J. Immunol. 177, 7131-7138
  10. Oda, T., Yoshie, H. and Yamazaki, K. (2003) Porphyromonas gingivalis antigen preferentially stimulates T cells to express IL-17 but not receptor activator of NF-kappaB ligand in vitro. Oral Microbiol. Immunol. 18, 30-36
  11. McAllister, F., Henry, A., Kreindler, J. L., Dubin, P. J., Ulrich, L., Steele, C., Finder, J. D., Pilewski, J. M., Carreno, B. M., Goldman, S. J., Pirhonen, J. and Kolls, J. K. (2005) Role of IL-17A, IL-17F, and the IL-17 receptor in regulating growth-related oncogene-alpha and granulocyte colony-stimulating factor in bronchial epithelium: implications for airway inflammation in cystic fibrosis. J. Immunol. 175, 404-412
  12. Maertzdorf, J., Osterhaus, A. D. and Verjans, G. M. (2002) IL-17 expression in human herpetic stromal keratitis: modulatory effects on chemokine production by corneal fibroblasts. J. Immunol. 169, 5897-5903
  13. Maek, A. N. W., Buranapraditkun, S., Klaewsongkram, J. and Ruxrungtham, K. (2007) Increased interleukin-17 production both in helper T cell subset Th17 and CD4-negative T cells in human immunodeficiency virus infection. Viral. Immunol. 20, 66-75
  14. Misse, D., Yssel, H., Trabattoni, D., Oblet, C., Lo Caputo, S., Mazzotta, F., Pene, J., Gonzalez, J. P., Clerici, M. and Veas, F. (2007) IL-22 participates in an innate anti-HIV-1 host-resistance network through acute-phase protein induction. J. Immunol. 178, 407-415
  15. Rowan, A. G., Fletcher, J. M., Ryan, E. J., Moran, B., Hegarty, J. E., O'Farrelly, C. and Mills, K. H. (2008) Hepatitis C virus-specific Th17 cells are suppressed by virus-induced TGF-beta. J. Immunol. 181, 4485-4494
  16. Yoshida, H. and Miyazaki, Y. (2008) Regulation of immune responses by interleukin-27. Immunol. Rev. 226, 234-247
  17. Zelante, T., De Luca, A., Bonifazi, P., Montagnoli, C., Bozza, S., Moretti,S., Belladonna, M. L., Vacca, C., Conte, C., Mosci, P., Bistoni, F., Puccetti,P., Kastelein, R. A., Kopf, M. and Romani, L. (2007) IL-23 and the Th17 pathway promote inflammation and impair antifungal immune resistance. Eur. J. Immunol. 37, 2695-2706
  18. Kim, B., Sarangi, P. P., Azkur, A. K., Kaistha, S. D. and Rouse, B. T. (2008) Enhanced viral immunoinflammatory lesions in mice lacking IL-23 responses. Microbes. Infect. 10, 302-312
  19. Dodon, M. D., Li, Z., Hamaia, S. and Gazzolo, L. (2004) Tax protein of human T-cell leukaemia virus type 1 induces interleukin 17 gene expression in T cells. J. Gen. Virol. 85, 1921-1932
  20. Chung, D. R., Kasper, D. L., Panzo, R. J., Chitnis, T., Grusby, M. J., Sayegh, M. H. and Tzianabos, A. O. (2003) CD4+ T cells mediate abscess formation in intra-abdominal sepsis by an IL-17-dependent mechanism. J. Immunol. 170, 1958-1963
  21. Kawakami, Y., Tomimori, Y., Yumoto, K., Hasegawa, S., Ando, T., Tagaya, Y., Crotty, S. and Kawakami, T. (2009) Inhibition of NK cell activity by IL-17 allows vaccinia virus to induce severe skin lesions in a mouse model of eczema vaccinatum. J. Exp. Med. 206, 1219-1225
  22. Mosmann, T. R. and Coffman, R. L. (1989) TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu. Rev. Immunol. 7, 145-173
  23. Peng, M. Y., Wang, Z. H., Yao, C. Y., Jiang, L. N., Jin, Q. L., Wang, J. and Li, B. Q. (2008) Interleukin 17-producing gamma delta T cells increased in patients with active pulmonary tuberculosis. Cell Mol. Immunol. 5, 203-208
  24. Kotloski, N. J., Nardelli, D. T., Peterson, S. H., Torrealba, J. R., Warner, T. F., Callister, S. M. and Schell, R. F. (2008) Interleukin-23 is required for development of arthritis in mice vaccinated and challenged with Borrelia Species. Clin. Vaccine Immunol. 15, 1199-1207
  25. Schulz, S. M., Kohler, G., Schutze, N., Knauer, J., Straubinger, R. K., Chackerian, A. A., Witte, E., Wolk, K., Sabat, R., Iwakura, Y., Holscher, C., Muller, U., Kastelein, R. A. and Alber, G. (2008) Protective immunity to systemic infection with attenuated Salmonella enterica serovar enteritidis in the absence of IL-12 is associated with IL-23-dependent IL-22, but not IL-17. J. Immunol. 181, 7891-7901
  26. Loures, F. V., Pina, A., Felonato, M. and Calich, V. L. (2009) TLR2 is a negative regulator of Th17 cells and tissue pathology in a pulmonary model of fungal infection. J. Immunol. 183, 1279-1290
  27. Anderson, C. F., Stumhofer, J. S., Hunter, C. A. and Sacks, D. (2009) IL-27 regulates IL-10 and IL-17 from CD4+ cells in nonhealing Leishmania major infection. J. Immunol. 183, 4619-4627
  28. Eyerich, K., Foerster, S., Rombold, S., Seidl, H. P., Behrendt H., Hofmann, H., Ring, J. and Traidl-Hoffmann, C. (2008) Patients with chronic mucocutaneous candidiasis exhibit reduced production of Th17-associated cytokines IL-17 and IL-22. J. Invest. Dermatol. 128, 2640-2645
  29. Infante-Duarte, C., Horton, H. F., Byrne, M. C. and Kamradt, T. (2000) Microbial lipopeptides induce the production of IL-17 in Th cells. J. Immunol. 165, 6107-6115
  30. Godinez, I., Raffatellu, M., Chu, H., Paixao, T. A., Haneda, T., Santos, R. L., Bevins, C. L., Tsolis, R. M. and Baumler, A. J. (2009) Interleukin-23 orchestrates mucosal responses to Salmonella enterica serotype Typhimurium in the intestine. Infect. Immun. 77, 387-398
  31. Intlekofer, A. M., Banerjee, A., Takemoto, N., Gordon, S. M., Dejong, C. S., Shin, H., Hunter, C. A., Wherry, E. J., Lindsten, T. and Reiner, S. L. (2008) Anomalous type 17 response to viral infection by CD8+ T cells lacking T-bet and eomesodermin. Science 321, 408-411
  32. Rutitzky, L. I., Lopes da Rosa, J. R. and Stadecker, M. J. (2005) Severe CD4 T cell-mediated immunopathology in murine schistosomiasis is dependent on IL-12p40 and correlates with high levels of IL-17. J. Immunol. 175, 3920- 3926
  33. Tallima, H., Salah, M., Guirguis, F. R. and El Ridi, R. (2009) Transforming growth factor-beta and Th17 responses in resistance to primary murine schistosomiasis mansoni. Cytokine. 48, 239-245
  34. Milner, J. D., Brenchley, J. M., Laurence, A., Freeman, A. F., Hill, B. J., Elias, K. M., Kanno, Y., Spalding, C., Elloumi, H. Z., Paulson, M. L., Davis, J., Hsu, A., Asher, A. I., O'Shea, J., Holland, S. M., Paul, W. E. and Douek, D. C. (2008) Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature 452, 773-776
  35. Rudner, X. L., Happel, K. I., Young, E. A. and Shellito, J. E. (2007) Interleukin-23 (IL-23)-IL-17 cytokine axis in murine Pneumocystis carinii infection. Infect. Immun. 75, 3055-3061
  36. Aujla, S. J., Chan, Y. R., Zheng, M., Fei, M., Askew, D. J., Pociask, D. A., Reinhart, T. A., McAllister, F., Edeal, J., Gaus, K., Husain, S., Kreindler, J. L., Dubin, P. J., Pilewski, J. M., Myerburg, M. M., Mason, C. A., Iwakura, Y. and Kolls, J. K. (2008) IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nat. Med. 14, 275-281
  37. Ivanov, II, Frutos Rde, L., Manel, N., Yoshinaga, K., Rifkin, D. B., Sartor, R. B., Finlay, B. B. and Littman, D. R. (2008) Specific microbiota direct the differentiation of IL-17-producing Thelper cells in the mucosa of the small intestine. Cell Host Microbe. 4, 337-349
  38. Raffatellu, M., Santos, R. L., Chessa, D., Wilson, R. P., Winter, S. E., Rossetti, C. A., Lawhon, S. D., Chu, H., Lau, T., Bevins, C. L., Adams, L. G. and Baumler, A. J. (2007) The capsule encoding the viaB locus reduces interleukin- 17 expression and mucosal innate responses in the bovine intestinal mucosa during infection with Salmonella enterica serotype Typhi. Infect. Immun. 75, 4342-4350
  39. Raffatellu, M., Santos, R. L., Verhoeven, D. E., George, M D., Wilson, R. P., Winter, S. E., Godinez, I., Sankaran, S., Paixao, T. A., Gordon, M. A., Kolls, J. K., Dandekar, S. and Baumler, A. J. (2008) Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut. Nat. Med. 14, 421-428
  40. Owyang, A. M., Zaph, C., Wilson, E. H., Guild, K. J., McClanahan, T., Miller, H. R., Cua, D. J., Goldschmidt, M., Hunter, C. A., Kastelein, R. A. and Artis, D. (2006) Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract. J. Exp. Med. 203, 843-849
  41. Happel, K. I., Zheng, M., Young, E., Quinton, L. J., Lockhart, E., Ramsay, A. J., Shellito, J. E., Schurr, J. R., Bagby, G. J., Nelson, S. and Kolls, J. K. (2003) Cutting edge: roles of Toll-like receptor 4 and IL-23 in IL-17 xpression in response to Klebsiella pneumoniae infection. J. Immunol. 170, 4432-4436
  42. Ma, C. S., Chew, G. Y., Simpson, N., Priyadarshi, A., Wong, M., Grimbacher, B., Fulcher, D. A., Tangye, S. G. and Cook, M. C. (2008) Deficiency of Th17 cells in hyper IgE syndrome due to mutations in STAT3. J. Exp. Med. 205, 1551-1557
  43. Molesworth-Kenyon, S. J., Yin, R., Oakes, J. E. and Lausch, R. N. (2008) IL-17 receptor signaling influences virus-induced corneal inflammation. J. Leukoc. Biol. 83, 401-408
  44. Kelly, M. N., Kolls, J. K., Happel, K., Schwartzman, J. D., Schwarzenberger, P., Combe, C., Moretto, M. and Khan, I. A. (2005) Interleukin-17/interleukin-17 receptor-mediated signaling is important for generation of an optimal polymorphonuclear response against Toxoplasma gondii infection. Infect. Immun. 73, 617-621
  45. Vargas-Inchaustegui, D. A., Xin, L. and Soong, L. (2008) Leishmania braziliensis infection induces dendritic cell activation, ISG15 transcription, and the generation of protective immune responses. J. Immunol. 180, 7537-7545
  46. Ehigiator, H. N., McNair, N. and Mead, J. R. (2007) Cryptosporidium parvum: the contribution of Th1-inducing pathways to the resolution of infection in mice. Exp. Parasitol. 115, 107-113
  47. Holland, S. M., DeLeo, F. R., Elloumi, H. Z., Hsu, A. P., Uzel, G., Brodsky, N., Freeman, A. F., Demidowich, A., Davis, J., Turner, M. L., Anderson, V. L., Darnell, D. N., Welch, P. A., Kuhns, D. B., Frucht, D. M., Malech, H. L., Gallin, J. I., Kobayashi, S. D., Whitney, A. R., Voyich, J. M., Musser, J. M., Woellner, C., Schaffer, A. A., Puck, J. M. and Grimbacher, B. (2007) STAT3 mutations in the hyper-IgE syndrome. N. Engl. J. Med. 357, 1608-1619
  48. Hamada, S., Umemura, M., Shiono, T., Hara, H., Kishihara, K., Tanaka, K., Mayuzumi, H., Ohta, T. and Matsuzaki, G. (2008) Importance of murine Vdelta1gammadelta T cells expressing interferon-gamma and interleukin-17A in innate protection against Listeria monocytogenes infection. Immunology 125, 170-177
  49. Kohyama, S., Ohno, S., Isoda, A., Moriya, O., Belladonna, M. L., Hayashi, H., Iwakura, Y., Yoshimoto, T., Akatsuka, T. and Matsui, M. (2007) IL-23 enhances host defense against vaccinia virus infection via a mechanism partly involving IL-17. J. Immunol. 179, 3917-3925
  50. Pitta, M. G., Romano, A., Cabantous, S., Henri, S., Hammad, A., Kouriba, B., Argiro, L., el Kheir, M., Bucheton, B., Mary, C., El-Safi, S. H. and Dessein, A. (2009) IL-17 and IL-22 are associated with protection against human kala azar caused by Leishmania donovani. J. Clin. Invest. 119, 2379-2387
  51. Monteiro, A. C., Schmitz, V., Morrot, A., de Arruda, L. B., Nagajyothi, F., Granato, A., Pesquero, J. B., Muller-Esterl, W., Tanowitz, H. B. and Scharfstein, J. (2007) Bradykinin B2 Receptors of dendritic cells, acting as sensors of kinins proteolytically released by Trypanosoma cruzi, are critical for the development of protective type-1 responses. PLoS Pathog. 3, e185
  52. Rutitzky, L. I. and Stadecker, M. J. (2006) CD4 T cells producing pro-inflammatory interleukin-17 mediate high pathology in schistosomiasis. Mem. Inst. Oswaldo. Cruz. 101(Suppl 1), 327-330
  53. Chan, Y. R., Liu, J. S., Pociask, D. A., Zheng, M., Mietzner, T. A., Berger, T., Mak, T. W., Clifton, M. C., Strong, R. K., Ray, P. and Kolls, J. K. (2009) Lipocalin 2 is required for pulmonary host defense against Klebsiella infection. J. Immunol. 182, 4947-4956
  54. Umemura, M., Yahagi, A., Hamada, S., Begum, M. D., Watanabe, H., Kawakami, K., Suda, T., Sudo, K., Nakae, S., Iwakura, Y. and Matsuzaki, G. (2007) IL-17-mediated regulation of innate and acquired immune response against pulmonary Mycobacterium bovis bacille Calmette-Guerin infection. J. Immunol. 178, 3786-3796
  55. Dubin, P. J. and Kolls, J. K. (2007) IL-23 mediates inflammatory responses to mucoid Pseudomonas aeruginosa lung infection in mice. Am. J. Physiol. Lung. Cell. Mol. Physiol. 292, L519-528
  56. Minegishi, Y., Saito, M., Nagasawa, M., Takada, H., Hara, T., Tsuchiya, S., Agematsu, K., Yamada, M., Kawamura, N., Ariga, T., Tsuge, I. and Karasuyama, H. (2009) Molecular explanation for the contradiction between systemic Th17 defect and localized bacterial infection in hyper-IgE syndrome. J. Exp. Med. 206, 1291-1301
  57. Ge, J., Wang, K., Meng, Q. H., Qi, Z. X., Meng, F. L. and Fan, Y. C. (2009) Implication of Th17 and Th1 Cells in Patients with Chronic Active Hepatitis B. J. Clin. Immunol
  58. McKinstry, K. K., Strutt, T. M., Buck, A., Curtis, J. D., Dibble, J. P., Huston, G., Tighe, M., Hamada, H., Sell, S., Dutton, R. W. and Swain, S. L. (2009) IL-10 deficiency unleashes an influenza-specific Th17 response and enhances survival against high-dose challenge. J. Immunol. 182, 7353-7363
  59. Stumhofer, J. S., Laurence, A., Wilson, E. H., Huang, E., Tato, C. M., Johnson, L. M., Villarino, A. V., Huang, Q., Yoshimura, A., Sehy, D., Saris, C. J., O'Shea, J. J., Hennighausen, L., Ernst, M. and Hunter, C. A. (2006) Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system. Nat. Immunol. 7, 937-945
  60. Burchill, M. A., Nardelli, D. T., England, D. M., DeCoster, D. J., Christopherson, J. A., Callister, S. M. and Schell, R. F. (2003) Inhibition of interleukin-17 prevents the development of arthritis in vaccinated mice challenged with Borrelia burgdorferi. Infect. Immun. 71, 3437-3442
  61. Yu, J. J., Ruddy, M. J., Wong, G. C., Sfintescu, C., Baker, P. J., Smith, J. B., Evans, R. T. and Gaffen, S. L. (2007) An essential role for IL-17 in preventing pathogen-initiated bone destruction: recruitment of neutrophils to inflamed bone requires IL-17 receptor-dependent signals. Blood 109, 3794-3802
  62. Martin, B., Hirota, K., Cua, D. J., Stockinger, B. and Veldhoen, M. (2009) Interleukin-17-producing gammadelta T cells selectively expand in response to pathogen products and environmental signals. Immunity 31, 321-330
  63. Petro, T. M. (2005) ERK-MAP-kinases differentially regulate expression of IL-23 p19 compared with p40 and IFN-beta in Theiler's virus-infected RAW264.7 cells. Immunol. Lett. 97, 47-53
  64. Robinson, M. J., Osorio, F., Rosas, M., Freitas, R. P., Schweighoffer, E., Gross, O., Verbeek, J. S., Ruland, J., Tybulewicz, V., Brown, G. D., Moita, L. F., Taylor, P. R. and Reis e Sousa, C. (2009) Dectin-2 is a Syk-coupled pattern ecognition receptor crucial for Th17 responses to fungal infection. J. Exp. Med. 206, 2037-2051
  65. Caruso, R., Fina, D., Paoluzi, O. A., Del Vecchio Blanco, G., Stolfi, C., Rizzo, A., Caprioli, F., Sarra, M., Andrei, F., Fantini, M. C., MacDonald, T. T., Pallone, F. and Monteleone, G. (2008) IL-23-mediated regulation of IL-17 production in Helicobacter pylori-infected gastric mucosa. Eur. J. Immunol. 38, 470-478
  66. Wu, Q., Martin, R. J., Rino, J. G., Breed, R., Torres, R. M. and Chu, H. W. (2007) IL-23-dependent IL-17 production is essential in neutrophil recruitment and activity in mouse lung defense against respiratory Mycoplasma pneumoniae infection. Microbes. Infect. 9, 78-86
  67. Hou, W., Kang, H. S. and Kim, B. S. (2009) Th17 cells enhance viral persistence and inhibit T cell cytotoxicity in a model of chronic virus infection. J. Exp. Med. 206, 313-328
  68. Locksley, R. M. (2009) Nine lives: plasticity among T helper cell subsets. J. Exp. Med. 206, 1643-1646
  69. Khader, S. A., Pearl, J. E., Sakamoto, K., Gilmartin, L., Bell, G. K., Jelley-Gibbs, D. M., Ghilardi, N., deSauvage, F. and Cooper, A. M. (2005) IL-23 compensates for the absence of IL-12p70 and is essential for the IL-17 response during tuberculosis but is dispensable for protection and antigen-specific IFN-gamma responses if IL-12p70 is available. J. Immunol. 175, 788-795
  70. Grimbacher, B., Holland, S. M., Gallin, J. I., Greenberg, F., Hill, S. C., Malech, H. L., Miller, J. A., O'Connell, A. C. and Puck, J. M. (1999) Hyper-IgE syndrome with recurrent infections--an autosomal dominant multisystem disorder. N. Engl. J. Med. 340, 692-702
  71. Huang, W., Na, L., Fidel, P. L. and Schwarzenberger, P. (2004) Requirement of interleukin-17A for systemic anti-Candida albicans host defense in mice. J. Infect. Dis. 190, 624-631
  72. Ferwerda, B., Ferwerda, G., Plantinga, T. S., Willment, J. A., van Spriel, A. B., Venselaar, H., Elbers, C. C., Johnson, M. D., Cambi, A., Huysamen, C., Jacobs, L., Jansen, T., Verheijen, K., Masthoff, L., Morre, S. A., Vriend, G., Williams, D. L., Perfect, J. R., Joosten, L. A., Wijmenga, C., van der Meer, J. W., Adema, G. J., Kullberg, B. J., Brown, G. D. and Netea, M. G. (2009) Human dectin-1 deficiency and mucocutaneous fungal infections. N. Engl. J. Med. 361, 1760-1767
  73. Knauer, J., Siegemund, S., Muller, U., Al-Robaiy, S., Kastelein, R. A., Alber, G. and Straubinger, R. K. (2007) Borrelia burgdorferi potently activates bone marrow-derived conventional dendritic cells for production of IL-23 required for IL-17 release by T cells. FEMS Immunol. Med. Microbiol. 49, 353-363
  74. Otani, K., Watanabe, T., Tanigawa, T., Okazaki, H., Yamagami, H., Watanabe, K., Tominaga, K., Fujiwara, Y., Oshitani, N. and Arakawa, T. (2009) Anti-inflammatory effects of IL-17A on Helicobacter pylori-induced gastritis. Biochem. Biophys. Res. Commun. 382, 252-258
  75. Conti, H. R., Shen, F., Nayyar, N., Stocum, E., Sun, J. N., Lindemann, M. J., Ho, A. W., Hai, J. H., Yu, J. J., Jung, J. W., Filler, S. G., Masso-Welch, P., Edgerton, M. and Gaffen, S. L. (2009) Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. J. Exp. Med. 206, 299-311
  76. Ye, P., Garvey, P. B., Zhang, P., Nelson, S., Bagby, G., Summer, W. R., Schwarzenberger, P., Shellito, J. E. and Kolls, J. K. (2001) Interleukin-17 and lung host defense against Klebsiella pneumoniae infection. Am. J. Respir. Cell. Mol. Biol. 25, 335-340
  77. Mills, K. H. (2001) Immunity to Bordetella pertussis. Microbes. Infect. 3, 655-677
  78. Ouyang, W., Kolls, J. K. and Zheng, Y. (2008) The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity 28, 454-467
  79. Ishigame, H., Kakuta, S., Nagai, T., Kadoki, M., Nambu, A., Komiyama, Y., Fujikado, N., Tanahashi, Y., Akitsu, A., Kotaki, H., Sudo, K., Nakae, S., Sasakawa, C. and Iwakura, Y. (2009) Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses. Immunity 30, 108-119
  80. Cruz, A., Khader, S. A., Torrado, E., Fraga, A., Pearl, J. E., Pedrosa, J., Cooper, A. M. and Castro, A. G. (2006) Cutting edge: IFN-gamma regulates the induction and expansion of IL-17-producing CD4 T cells during mycobacterial infection. J. Immunol. 177, 1416-1420
  81. Stern, R. C. (1997) The diagnosis of cystic fibrosis. N. Engl. J. Med. 336, 487-491
  82. Wiehler, S. and Proud, D. (2007) Interleukin-17A modulates human airway epithelial responses to human rhinovirus infection. Am. J. Physiol. Lung. Cell. Mol. Physiol. 293, L505-515
  83. Codolo, G., Amedei, A., Steere, A. C., Papinutto, E., Cappon, A., Polenghi, A., Benagiano, M., Paccani, S. R., Sambri, V., Del Prete, G., Baldari, C. T., Zanotti, G., Montecucco, C., D'Elios, M. M. and de Bernard, M. (2008) Borrelia burgdorferi NapA-driven Th17 cell inflammation in lyme arthritis. Arthritis. Rheum. 58, 3609-3617
  84. Algood, H. M., Allen, S. S., Washington, M. K., Peek, R. M., Jr., Miller, G. G. and Cover, T. L. (2009) Regulation of gastric b cell recruitment is dependent on IL-17 receptor a signaling in a model of chronic bacterial infection. J. Immunol. 183, 5837-5846
  85. Zheng, Y., Valdez, P. A., Danilenko, D. M., Hu, Y., Sa, S. M., Gong, Q., Abbas, A. R., Modrusan, Z., Ghilardi, N., de Sauvage, F. J. and Ouyang, W. (2008) Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat. Med. 14, 282-289
  86. Ivanov, II, Atarashi, K., Manel, N., Brodie, E. L., Shima, T., Karaoz, U., Wei, D., Goldfarb, K. C., Santee, C. A., Lynch, S. V., Tanoue, T., Imaoka, A., Itoh, K., Takeda, K., Umesaki, Y., Honda, K. and Littman, D. R. (2009) Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell. 139, 485-498
  87. Priebe, G. P., Walsh, R. L., Cederroth, T. A., Kamei, A., Coutinho-Sledge, Y. S., Goldberg, J. B. and Pier, G. B. (2008) IL-17 is a critical component of vaccine-induced protection against lung infection by lipopolysaccharideheterologous strains of Pseudomonas aeruginosa. J. Immunol. 181, 4965-4975
  88. Glocker, E. O., Hennigs, A., Nabavi, M., Schaffer, A. A., Woellner, C., Salzer, U., Pfeifer, D., Veelken, H., Warnatz, K., Tahami, F., Jamal, S., Manguiat, A., Rezaei, N., Amirzargar, A. A., Plebani, A., Hannesschlager, N., Gross, O., Ruland, J. and Grimbacher, B. (2009) A homozygous CARD9 mutation in a family with susceptibility to fungal infections. N. Engl. J. Med. 361, 1727-1735
  89. Aujla, S. J., Dubin, P. J. and Kolls, J. K. (2007) Th17 cells and mucosal host defense. Semin. Immunol. 19, 377-382
  90. Lockhart, E., Green, A. M. and Flynn, J. L. (2006) IL-17 production is dominated by gammadelta T cells rather than CD4 T cells during Mycobacterium tuberculosis infection. J. Immunol. 177, 4662-4669
  91. Hamada, S., Umemura, M., Shiono, T., Tanaka, K., Yahagi, A., Begum, M. D., Oshiro, K., Okamoto, Y., Watanabe, H., Kawakami, K., Roark, C., Born, W. K., O'Brien, R., Ikuta, K., Ishikawa, H., Nakae, S., Iwakura, Y., Ohta, T. and Matsuzaki, G. (2008) IL-17A produced by gammadelta T cells plays a critical role in innate immunity against listeria monocytogenes infection in the liver. J. Immunol. 181, 3456-3463
  92. Shibata, K., Yamada, H., Hara, H., Kishihara, K. and Yoshikai, Y. (2007) Resident Vdelta1+ gammadelta T cells control early infiltration of neutrophils after Escherichia coli infection via IL-17 production. J. Immunol. 178, 4466-4472
  93. Patera, A. C., Pesnicak, L., Bertin, J. and Cohen, J. I. (2002) Interleukin 17 modulates the immune response to vaccinia virus infection. Virology 299, 56-63
  94. Park, H., Li, Z., Yang, X. O., Chang, S. H., Nurieva, R., Wang, Y. H., Wang, Y., Hood, L., Zhu, Z., Tian, Q. and Dong, C. (2005) A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat. Immunol. 6, 1133-1141
  95. van de Veerdonk, F. L., Marijnissen, R. J., Kullberg, B. J., Koenen, H. J., Cheng, S. C., Joosten, I., van den Berg, W. B., Williams, D. L., van der Meer, J. W., Joosten, L. A. and Netea, M. G. (2009) The macrophage mannose receptor induces IL-17 in response to Candida albicans. Cell Host Microbe 5, 329-340
  96. LeibundGut-Landmann, S., Gross, O., Robinson, M. J., Osorio, F., Slack, E. C., Tsoni, S. V., Schweighoffer, E., Tybulewicz, V., Brown, G. D., Ruland, J. and Reis e Sousa, C. (2007) Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17. Nat. Immunol. 8, 630-638
  97. Kleinschek, M. A., Muller, U., Brodie, S. J., Stenzel, W., Kohler, G., Blumenschein, W. M., Straubinger, R. K., McClanahan, T., Kastelein, R. A. and Alber, G. (2006) IL-23 enhances the inflammatory cell response in Cryptococcus neoformans infection and induces a cytokine pattern distinct from IL-12. J. Immunol. 176, 1098-1106
  98. Happel, K. I., Dubin, P. J., Zheng, M., Ghilardi, N., Lockhart, C., Quinton, L. J., Odden, A. R., Shellito, J. E., Bagby, G. J., Nelson, S. and Kolls, J. K. (2005) Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae. J. Exp. Med. 202, 761-769
  99. Zenewicz, L. A., Yancopoulos, G. D., Valenzuela, D. M., Murphy, A. J., Karow, M. and Flavell, R. A. (2007) Interleukin-22 but not interleukin-17 provides protection to hepatocytes during acute liver inflammation. Immunity 27, 647-659
  100. Oyoshi, M. K., Elkhal, A., Kumar, L., Scott, J. E., Koduru, S., He, R., Leung, D. Y., Howell, M. D., Oettgen, H. C., Murphy, G. F. and Geha, R. S. (2009) Vaccinia virus inoculation in sites of allergic skin inflammation elicits a vigorous cutaneous IL-17 response. Proc. Natl. Acad. Sci. U.S.A. 106, 14954-14959

Cited by

  1. Novel Approach for Improved Assessment of Phenotypic and Functional Characteristics of BKV-Specific T-Cell Immunity vol.92, pp.11, 2011,
  2. The Th1/Th2/Th17 cytokine profile of HIV-infected individuals: A multivariate cytokinomics approach vol.61, pp.2, 2013,
  3. Designing polymeric particles for antigen delivery vol.40, pp.1, 2011,
  4. Each type of cause that initiates rheumatoid arthritis or RA flares differentially affects the response to therapy vol.78, pp.1, 2012,
  5. Impaired Notch-MKP-1 signalling in hidradenitis suppurativa: an approach to pathogenesis by evidence from translational biology vol.22, pp.3, 2013,
  6. IL-17A promotes transdifferentiation of mouse myoblast cells (C2C12) into adipocytes by increasing the expression of peroxisome proliferator-activated receptor γ through CAAT/enhancer binding protein β signaling vol.33, pp.2, 2011,
  7. Altered Host-Microbe Interaction in HIV: A Target for Intervention with Pro- and Prebiotics vol.29, pp.5, 2010,
  8. Variation in human genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese vol.13, pp.6, 2012,
  9. IL-1β/IL-6/CRP and IL-18/ferritin: Distinct Inflammatory Programs in Infections vol.12, pp.12, 2016,
  10. Characterization of host immunity during persistent vaginal colonization by Group B Streptococcus vol.8, pp.6, 2015,
  11. Polymorphisms in CCR6 Are Associated with Chronic Graft-versus-Host Disease and Invasive Fungal Disease in Matched-Related Hematopoietic Stem Cell Transplantation vol.17, pp.10, 2011,
  12. IRIS and Fungal Infections: What Have We Learned? vol.6, pp.1, 2012,
  13. Unravelling fungal immunity through primary immune deficiencies vol.15, pp.4, 2012,
  14. Pathogenesis and control of the Chinese highly pathogenic porcine reproductive and respiratory syndrome virus 2017,
  15. Intermittent preventive treatment with sulfadoxine-pyrimethamine does not modify plasma cytokines and chemokines or intracellular cytokine responses to Plasmodium falciparum in Mozambican Children vol.13, pp.1, 2012,
  16. Sunset yellow FCF, a permitted food dye, alters functional responses of splenocytes at non-cytotoxic dose vol.217, pp.3, 2013,
  17. Identification and functional characterization of the house finch interleukin-1β vol.69, 2017,
  18. Development of experimental cerebral malaria is independent of IL-23 and IL-17 vol.402, pp.4, 2010,
  19. Immediate T-Helper 17 Polarization Upon Triggering CD11b/c on HIV-Exposed Dendritic Cells vol.212, pp.1, 2015,
  20. Analysis of the mucosal immune responses induced by single and trickle infections with the bovine abomasal nematodeOstertagia ostertagi vol.36, pp.4, 2014,
  21. The classical CD14++CD16− monocytes, but not the patrolling CD14+CD16+ monocytes, promote Th17 responses to Candida albicans vol.41, pp.10, 2011,
  22. Inducible NO synthase and antibacterial host defence in times of Th17/Th22/T22 immunity vol.13, pp.3, 2011,
  23. Immunoresponses in dermatomycoses vol.42, pp.3, 2015,
  24. Toll-like receptor 2 induced cytotoxic T-lymphocyte-associated protein 4 regulates Aspergillus-induced regulatory T-cells with pro-inflammatory characteristics vol.7, pp.1, 2017,
  25. Inflammatory fibroblasts in cancer vol.39, pp.8, 2016,
  26. CNS-specific Therapy for Ongoing EAE by Silencing IL-17 Pathway in Astrocytes vol.20, pp.7, 2012,
  27. RNA-seq analysis reveals significant transcriptome changes in turbot (Scophthalmus maximus) suffering severe enteromyxosis vol.15, pp.1, 2014,
  28. Are Th17 Cells Playing a Role in Immunity to Dermatophytosis? vol.182, pp.1-2, 2017,
  29. Induced Treg Cells Augment the Th17-Mediated Intestinal Inflammatory Response in a CTLA4-Dependent Manner vol.11, pp.3, 2016,
  30. Optimal clearance of Sporothrix schenckii requires an intact Th17 response in a mouse model of systemic infection vol.220, pp.8, 2015,
  31. Rhinovirus inhibits IL-17A and the downstream immune responses in allergic asthma vol.9, pp.5, 2016,
  32. The complex pathogenesis of bacteremia vol.5, pp.1, 2014,
  33. Characterization of Th17 responses to Streptococcus pneumoniae in humans: Comparisons between adults and children in a developed and a developing country vol.30, pp.26, 2012,
  34. Differential induction of IL-17, IL-10, and IL-9 in human T helper cells by B7h and B7.1 vol.64, pp.1, 2013,
  35. Invasive fungal infections in congenital immunodeficiencies vol.16, pp.9, 2010,
  36. Co-expression of S. Typhi GroEL and IL-22 gene augments immune responses against Salmonella infection vol.91, pp.10, 2013,
  37. Cryptococcus gattii Induces a Cytokine Pattern That Is Distinct from Other Cryptococcal Species vol.8, pp.1, 2013,
  38. Is IL-17 an accomplice contributing to salivary gland damage during CMV infection? vol.8, pp.9, 2013,
  39. Th17 Cells Are Involved in the Local Control of Tumor Progression in Primary Intraocular Lymphoma vol.6, pp.9, 2011,
  40. Evolutionary Insights into IL17A in Lagomorphs vol.2015, 2015,
  41. Ecdysone triggered PGRP-LC expression controls Drosophila innate immunity vol.32, pp.11, 2013,
  42. Elevated Cerebrospinal Fluid Interleukin-17A and Interferon-γ Levels in Early Asymptomatic Neurosyphilis vol.40, pp.10, 2013,
  43. T helper type 2 bias and type 17 suppression in primary dengue virus infection in infants and young children vol.107, pp.7, 2013,
  44. Microbiota and Probiotics in Health and HIV Infection vol.9, pp.6, 2017,
  45. A Murine Inhalation Model to Characterize Pulmonary Exposure to Dry Aspergillus fumigatus Conidia vol.9, pp.10, 2014,
  46. Safety and Protective Effectiveness of Two Strains of Lactobacillus with Probiotic Features in an Experimental Model of Salmonellosis vol.11, pp.9, 2014,
  47. Pasteurella multocida Toxin Manipulates T Cell Differentiation vol.6, 2015,
  48. Immunonutritional diet modulates natural killer cell activation and Th17 cell distribution in patients with gastric and esophageal cancer vol.27, pp.2, 2011,
  49. Th2 and Th9 responses in patients with chronic mucocutaneous candidiasis and hyper-IgE syndrome vol.46, pp.12, 2016,
  50. Syk-coupled C-type lectins in immunity vol.32, pp.4, 2011,
  51. Nocardia brasiliensis Induces an Immunosuppressive Microenvironment That Favors Chronic Infection in BALB/c Mice vol.80, pp.7, 2012,
  52. Black Yeasts and Their Filamentous Relatives: Principles of Pathogenesis and Host Defense vol.27, pp.3, 2014,
  53. The Multifaceted Role of T-Helper Responses in Host Defense against Aspergillus fumigatus vol.3, pp.4, 2017,
  54. infection in cancer-associated fibroblast-induced epithelial-mesenchymal transition in vitro vol.23, pp.6, 2018,
  55. Individual variation is the key to the development of a vaccine against Staphylococcus aureus: a comparative study between mice lineages vol.51, pp.5, 2018,