Defective IL-17- and IL-22-dependent mucosal host response to Candida albicans determines susceptibility to oral candidiasis in mice expressing the HIV-1 transgene

BMC Immunology

Louis de Repentigny¹  Paul Jolicoeur²  Zaher Hanna²  Louis Gaboury³  Serge Sénéchal¹  Francine Aumont¹  Vincent Cousineau-Côté¹  Mathieu Goupil¹ 

[1] Department of Microbiology, Infectious Diseases and Immunology, Faculty of Medicine, University of Montreal, C.P. 6128, succursale Centre-Ville, Montreal H3C 3J7, Quebec, Canada;Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada;Histology and Molecular Pathology research unit, Institute for Research in Immunology and Cancer, C.P. 6128, succursale Centre-Ville, Montreal H3C 3J7, QC, Canada

关键词: Transgenic mice;    HIV-1;    IL-22;    IL-17;    Th17;    CD4+ T-cells;    Candida albicans;   

Others  :  1077685
DOI  :  10.1186/s12865-014-0049-9

 received in 2014-04-09, accepted in 2014-10-16,  发布年份 2014

【 摘 要 】

Background

The tissue-signaling cytokines IL-17 and IL-22 are critical to host defense against oral Candida albicans infection, by their induction of oral antimicrobial peptide expression and recruitment of neutrophils. Mucosal Th17 cells which produce these cytokines are preferentially depleted in HIV-infected patients. Here, we tested the hypothesis that defective IL-17- and IL-22-dependent host responses to C. albicans determine the phenotype of susceptibility to oropharyngeal candidiasis (OPC) in transgenic (Tg) mice expressing HIV-1.

Results

Naïve CD4+ T-cells and the differentiated Th1, Th2, Th17, Th1Th17 and Treg lineages were all profoundly depleted in cervical lymph nodes (CLNs) of these Tg mice. However, naive CD4+ cells from Tg mice maintained the capacity to differentiate into these lineages in response to polarizing cytokines in vitro. Expression of Il17, Il22, S100a8 and Ccl20 was enhanced in oral mucosal tissue of non-Tg, but not of Tg mice, after oral infection with C. albicans. Treatment of infected Tg mice with the combination of IL-17 and IL-22, but not IL-17 or Il-22 alone, significantly reduced oral burdens of C. albicans and abundance of Candida hyphae in the epithelium of tongues of infected Tg mice, and restored the ability of the Tg mice to up-regulate expression of S100a8 and Ccl20 in response to C. albicans infection.

Conclusions

These findings demonstrate that defective IL-17- and IL-22-dependent induction of innate mucosal immunity to C. albicans is central to the phenotype of susceptibility to OPC in these HIV transgenic mice.

【 授权许可】

   
2014 Goupil et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Samaranayake LP, Holmstrup P: Oral candidiasis and human immunodeficiency virus infection. J Oral Pathol Med 1989, 18(10):554-564.
• [2]Martins MD, Lozano-Chiu M, Rex JH: Declining rates of oropharyngeal candidiasis and carriage of Candida albicans associated with trends toward reduced rates of carriage of fluconazole-resistant C. albicans in human immunodeficiency virus-infected patients. Clin Infect Dis 1998, 27(5):1291-1294.
• [3]Sud N, Shanker V, Sharma A, Sharma NL, Gupta M: Mucocutaneous manifestations in 150 HIV-infected Indian patients and their relationship with CD4 lymphocyte counts. Int J STD AIDS 2009, 20(11):771-774.
• [4]Ranganathan K, Hemalatha R: Oral lesions in HIV infection in developing countries: an overview. Adv Dent Res 2006, 19(1):63-68.
• [5]Fabian FM, Kahabuka FK, Petersen PE, Shubi FM, Jurgensen N: Oral manifestations among people living with HIV/AIDS in Tanzania. Int Dent J 2009, 59(4):187-191.
• [6]de Repentigny L, Lewandowski D, Jolicoeur P: Immunopathogenesis of oropharyngeal candidiasis in human immunodeficiency virus infection. Clin Microbiol Rev 2004, 17(4):729-759. table of contents
• [7]Fidel PL Jr: Candida-host interactions in HIV disease: relationships in oropharyngeal candidiasis. Adv Dent Res 2006, 19(1):80-84.
• [8]Campo J, Del Romero J, Castilla J, Garcia S, Rodriguez C, Bascones A: Oral candidiasis as a clinical marker related to viral load, CD4 lymphocyte count and CD4 lymphocyte percentage in HIV-infected patients. J Oral Pathol Med 2002, 31(1):5-10.
• [9]Mercante DE, Leigh JE, Lilly EA, McNulty K, Fidel PL Jr: Assessment of the association between HIV viral load and CD4 cell count on the occurrence of oropharyngeal candidiasis in HIV-infected patients. J Acquir Immune Defic Syndr 2006, 42(5):578-583.
• [10]Nielsen H, Bentsen KD, Hojtved L, Willemoes EH, Scheutz F, Schiodt M, Stoltze K, Pindborg JJ: Oral candidiasis and immune status of HIV-infected patients. J Oral Pathol Med 1994, 23(3):140-143.
• [11]Conti HR, Shen F, Nayyar N, Stocum E, Sun JN, Lindemann MJ, Ho AW, Hai JH, Yu JJ, Jung JW, Filler SG, Masso-Welch P, Edgerton M, Gaffen SL: Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. J Exp Med 2009, 206(2):299-311.
• [12]Saunus JM, Wagner SA, Matias MA, Hu Y, Zaini ZM, Farah CS: Early activation of the interleukin-23-17 axis in a murine model of oropharyngeal candidiasis. Mol Oral Microbiol 2010, 25(5):343-356.
• [13]De Luca A, Zelante T, D’Angelo C, Zagarella S, Fallarino F, Spreca A, Iannitti RG, Bonifazi P, Renauld JC, Bistoni F, Puccetti P, Romani L: IL-22 defines a novel immune pathway of antifungal resistance. Mucosal Immunol 2010, 3(4):361-373.
• [14]Eyerich S, Wagener J, Wenzel V, Scarponi C, Pennino D, Albanesi C, Schaller M, Behrendt H, Ring J, Schmidt-Weber CB, Cavani A, Mempel M, Traidl-Hoffmann C, Eyerich K: IL-22 and TNF-alpha represent a key cytokine combination for epidermal integrity during infection with Candida albicans. Eur J Immunol 2011, 41(7):1894-1901.
• [15]Liang SC, Tan XY, Luxenberg DP, Karim R, Dunussi-Joannopoulos K, Collins M, Fouser LA: Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 2006, 203(10):2271-2279.
• [16]Wolk K, Witte E, Witte K, Warszawska K, Sabat R: Biology of interleukin-22. Semin Immunopathol 2010, 32(1):17-31.
• [17]Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R: IL-22 increases the innate immunity of tissues. Immunity 2004, 21(2):241-254.
• [18]Kolls JK, McCray PB Jr, Chan YR: Cytokine-mediated regulation of antimicrobial proteins. Nat Rev Immunol 2008, 8(11):829-835.
• [19]Peck A, Mellins ED: Precarious balance: Th17 cells in host defense. Infect Immun 2010, 78(1):32-38.
• [20]van de Veerdonk FL, Marijnissen RJ, Kullberg BJ, Koenen HJ, Cheng SC, Joosten I, van den Berg WB, Williams DL, van der Meer JW, Joosten LA, Netea MG: The macrophage mannose receptor induces IL-17 in response to Candida albicans. Cell Host Microbe 2009, 5(4):329-340.
• [21]Netea MG, Marodi L: Innate immune mechanisms for recognition and uptake of Candida species. Trends Immunol 2010, 31(9):346-353.
• [22]LeibundGut-Landmann S, Gross O, Robinson MJ, Osorio F, Slack EC, Tsoni SV, Schweighoffer E, Tybulewicz V, Brown GD, Ruland J, Reis e Sousa C: Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17. Nat Immunol 2007, 8(6):630-638.
• [23]Drummond RA, Saijo S, Iwakura Y, Brown GD: The role of Syk/CARD9 coupled C-type lectins in antifungal immunity. Eur J Immunol 2011, 41(2):276-281.
• [24]Robinson MJ, Osorio F, Rosas M, Freitas RP, Schweighoffer E, Gross O, Verbeek JS, Ruland J, Tybulewicz V, Brown GD, Moita LF, Taylor PR, Reis e Sousa C: Dectin-2 is a Syk-coupled pattern recognition receptor crucial for Th17 responses to fungal infection. J Exp Med 2009, 206(9):2037-2051.
• [25]Acosta-Rodriguez EV, Rivino L, Geginat J, Jarrossay D, Gattorno M, Lanzavecchia A, Sallusto F, Napolitani G: Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol 2007, 8(6):639-646.
• [26]Liu Y, Yang B, Zhou M, Li L, Zhou H, Zhang J, Chen H, Wu C: Memory IL-22-producing CD4+ T cells specific for Candida albicans are present in humans. Eur J Immunol 2009, 39(6):1472-1479.
• [27]Elhed A, Unutmaz D: Th17 cells and HIV infection. Curr Opin HIV AIDS 2010, 5(2):146-150.
• [28]El Hed A, Khaitan A, Kozhaya L, Manel N, Daskalakis D, Borkowsky W, Valentine F, Littman DR, Unutmaz D: Susceptibility of human Th17 cells to human immunodeficiency virus and their perturbation during infection. J Infect Dis 2010, 201(6):843-854.
• [29]Gosselin A, Monteiro P, Chomont N, Diaz-Griffero F, Said EA, Fonseca S, Wacleche V, El-Far M, Boulassel MR, Routy JP, Sekaly RP, Ancuta P: Peripheral blood CCR4 + CCR6+ and CXCR3 + CCR6 + CD4+ T cells are highly permissive to HIV-1 infection. J Immunol 2010, 184(3):1604-1616.
• [30]Prendergast A, Prado JG, Kang YH, Chen F, Riddell LA, Luzzi G, Goulder P, Klenerman P: HIV-1 infection is characterized by profound depletion of CD161+ Th17 cells and gradual decline in regulatory T cells. Aids 2010, 24(4):491-502.
• [31]Hu H, Nau M, Ehrenberg P, Chenine AL, Macedo C, Zhou Y, Daye ZJ, Wei Z, Vahey M, Michael NL, Kim JH, Marovich M, Ratto-Kim S: Distinct gene-expression profiles associated with the susceptibility of pathogen-specific CD4 T cells to HIV-1 infection. Blood 2013, 121(7):1136-1144.
• [32]Brenchley JM, Paiardini M, Knox KS, Asher AI, Cervasi B, Asher TE, Scheinberg P, Price DA, Hage CA, Kholi LM, Khoruts A, Frank I, Else J, Schacker T, Silvestri G, Douek DC: Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood 2008, 112(7):2826-2835.
• [33]Bixler SL, Mattapallil JJ: Loss and dysregulation of Th17 cells during HIV infection. Clinical dev Immunol 2013, 2013:852418.
• [34]Kim CJ, McKinnon LR, Kovacs C, Kandel G, Huibner S, Chege D, Shahabi K, Benko E, Loutfy M, Ostrowski M, Kaul R: Mucosal Th17 cell function is altered during HIV infection and is an independent predictor of systemic immune activation. J Immunol 2013, 191(5):2164-2173.
• [35]Hernandez-Santos N, Gaffen SL: Th17 cells in immunity to Candida albicans. Cell Host Microbe 2012, 11(5):425-435.
• [36]Conti HR, Gaffen SL: Host responses to Candida albicans: Th17 cells and mucosal candidiasis. Microbes Infect 2010, 12(7):518-527.
• [37]Weindl G, Wagener J, Schaller M: Epithelial cells and innate antifungal defense. J Dent Res 2010, 89(7):666-675.
• [38]Khader SA, Gaffen SL, Kolls JK: Th17 cells at the crossroads of innate and adaptive immunity against infectious diseases at the mucosa. Mucosal Immunol 2009, 2(5):403-411.
• [39]de Repentigny L, Aumont F, Ripeau JS, Fiorillo M, Kay DG, Hanna Z, Jolicoeur P: Mucosal candidiasis in transgenic mice expressing human immunodeficiency virus type 1. J Infect Dis 2002, 185(8):1103-1114.
• [40]Lewandowski D, Marquis M, Aumont F, Lussier-Morin AC, Raymond M, Senechal S, Hanna Z, Jolicoeur P, de Repentigny L: Altered CD4+ T cell phenotype and function determine the susceptibility to mucosal candidiasis in transgenic mice expressing HIV-1. J Immunol 2006, 177(1):479-491.
• [41]Hanna Z, Priceputu E, Chrobak P, Hu C, Dugas V, Goupil M, Marquis M, de Repentigny L, Jolicoeur P: Selective expression of human immunodeficiency virus Nef in specific immune cell populations of transgenic mice is associated with distinct AIDS-like phenotypes. J Virol 2009, 83(19):9743-9758.
• [42]Poudrier J, Weng X, Kay DG, Hanna Z, Jolicoeur P: The AIDS-like disease of CD4C/human immunodeficiency virus transgenic mice is associated with accumulation of immature CD11bHi dendritic cells. J Virol 2003, 77(21):11733-11744.
• [43]Espinosa V, Rivera A: Cytokines and the regulation of fungus-specific CD4 T cell differentiation. Cytokine 2012, 58(1):100-106.
• [44]Akdis M, Palomares O, van de Veen W, van Splunter M, Akdis CA: TH17 and TH22 cells: a confusion of antimicrobial response with tissue inflammation versus protection. J Allergy Clin Immunol 2012, 129(6):1438-1449.
• [45]McGeachy MJ, McSorley SJ: Microbial-induced Th17: superhero or supervillain? J Immunol 2012, 189(7):3285-3291.
• [46]Glocker EO, Grimbacher B: Mucosal antifungal defence: IL-17 signalling takes centre stage. Immunol Cell Biol 2011, 89(8):823-825.
• [47]Alvarez Y, Tuen M, Shen G, Nawaz F, Arthos J, Wolff MJ, Poles MA, Hioe CE: Preferential HIV infection of CCR6+ Th17 cells is associated with higher levels of virus receptor expression and lack of CCR5 ligands. J Virol 2013, 87(19):10843-10854.
• [48]He Y, Li J, Zheng Y, Luo Y, Zhou H, Yao Y, Chen X, Chen Z, He M: A randomized case–control study of dynamic changes in peripheral blood Th17/Treg cell balance and interleukin-17 levels in highly active antiretroviral-treated HIV type 1/AIDS patients. AIDS Res Hum Retrovir 2012, 28(4):339-345.
• [49]Peng Q, Wang H, Wang H, Li X, Lu X, Liu L, Zhou B, Chen Z: Imbalances of gut-homing CD4+ T-cell subsets in HIV-1-infected Chinese patients. J Acquir Immune Defic Syndr 2013, 64(1):25-31.
• [50]Cassone A, Cauda R: Candida and candidiasis in HIV-infected patients: where commensalism, opportunistic behavior and frank pathogenicity lose their borders. Aids 2012, 26(12):1457-1472.
• [51]Pirofski LA, Casadevall A: Rethinking T cell immunity in oropharyngeal candidiasis. J Exp Med 2009, 206(2):269-273.
• [52]Hanna Z, Kay DG, Rebai N, Guimond A, Jothy S, Jolicoeur P: Nef harbors a major determinant of pathogenicity for an AIDS-like disease induced by HIV-1 in transgenic mice. Cell 1998, 95(2):163-175.
• [53]Chrobak P, Simard MC, Bouchard N, Ndolo TM, Guertin J, Hanna Z, Dave V, Jolicoeur P: HIV-1 Nef disrupts maturation of CD4+ T cells through CD4/Lck modulation. J Immunol 2010, 185(7):3948-3959.
• [54]Weng X, Priceputu E, Chrobak P, Poudrier J, Kay DG, Hanna Z, Mak TW, Jolicoeur P: CD4+ T cells from CD4C/HIVNef transgenic mice show enhanced activation in vivo with impaired proliferation in vitro but are dispensable for the development of a severe AIDS-like organ disease. J Virol 2004, 78(10):5244-5257.
• [55]Chrobak P, Afkhami S, Priceputu E, Poudrier J, Meunier C, Hanna Z, Sparwasser T, Jolicoeur P: HIV Nef expression favors the relative preservation of CD4+ T regulatory cells that retain some important suppressive functions. J Immunol 2014, 192(4):1681-1692.
• [56]Chevalier MF, Petitjean G, Dunyach-Remy C, Didier C, Girard PM, Manea ME, Campa P, Meyer L, Rouzioux C, Lavigne JP, Barré-Sinoussi F, Scott-Algara D, Weiss L: The Th17/Treg ratio, IL-1RA and sCD14 levels in primary HIV infection predict the T-cell activation set point in the absence of systemic microbial translocation. PLoS Pathog 2013, 9(6):e1003453.
• [57]Rueda CM, Velilla PA, Chougnet CA, Montoya CJ, Rugeles MT: HIV-induced T-cell activation/exhaustion in rectal mucosa is controlled only partially by antiretroviral treatment. PLoS One 2012, 7(1):e30307.
• [58]Schulze Zur Wiesch J, Thomssen A, Hartjen P, Toth I, Lehmann C, Meyer-Olson D, Colberg K, Frerk S, Babikir D, Schmiedel S, Degen O, Mauss S, Rockstroh J, Staszewski S, Khaykin P, Strasak A, Lohse AW, Fätkenheuer G, Hauber J, van Lunzen J: Comprehensive analysis of frequency and phenotype of T regulatory cells in HIV infection: CD39 expression of FoxP3+ T regulatory cells correlates with progressive disease. J Virol 2011, 85(3):1287-1297.
• [59]Arruvito L, Sabatte J, Pandolfi J, Baz P, Billordo LA, Lasala MB, Salomon H, Geffner J, Fainboim L: Analysis of suppressor and non-suppressor FOXP3+ T cells in HIV-1-infected patients. PLoS One 2012, 7(12):e52580.
• [60]Moreno-Fernandez ME, Presicce P, Chougnet CA: Homeostasis and function of regulatory T cells in HIV/SIV infection. J Virol 2012, 86(19):10262-10269.
• [61]Chase AJ, Sedaghat AR, German JR, Gama L, Zink MC, Clements JE, Siliciano RF: Severe depletion of CD4+ CD25+ regulatory T cells from the intestinal lamina propria but not peripheral blood or lymph nodes during acute simian immunodeficiency virus infection. J Virol 2007, 81(23):12748-12757.
• [62]Roederer M, Dubs JG, Anderson MT, Raju PA, Herzenberg LA, Herzenberg LA: CD8 naive T cell counts decrease progressively in HIV-infected adults. J Clin Invest 1995, 95(5):2061-2066.
• [63]Sieg SF, Bazdar DA, Lederman MM: Impaired TCR-mediated induction of Ki67 by naive CD4+ T cells is only occasionally corrected by exogenous IL-2 in HIV-1 infection. J Immunol 2003, 171(10):5208-5214.
• [64]Rodriguez B, Bazdar DA, Funderburg N, Asaad R, Luciano AA, Yadavalli G, Kalayjian RC, Lederman MM, Sieg SF: Frequencies of FoxP3+ naive T cells are related to both viral load and naive T cell proliferation responses in HIV disease. J Leukoc Biol 2011, 90(3):621-628.
• [65]Liu Y, Yang B, Ma J, Wang H, Huang F, Zhang J, Chen H, Wu C: Interleukin-21 induces the differentiation of human Tc22 cells via phosphorylation of signal transducers and activators of transcription. Immunology 2011, 132(4):540-548.
• [66]Wurster AL, Rodgers VL, Satoskar AR, Whitters MJ, Young DA, Collins M, Grusby MJ: Interleukin 21 is a T helper (Th) cell 2 cytokine that specifically inhibits the differentiation of naive Th cells into interferon gamma-producing Th1 cells. J Exp Med 2002, 196(7):969-977.
• [67]Pallikkuth S, Parmigiani A, Pahwa S: The role of interleukin-21 in HIV infection. Cytokine Growth Factor Rev 2012, 23(4–5):173-180.
• [68]Nurieva R, Yang XO, Martinez G, Zhang Y, Panopoulos AD, Ma L, Schluns K, Tian Q, Watowich SS, Jetten AM, Dong C: Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 2007, 448(7152):480-483.
• [69]Varin A, Manna SK, Quivy V, Decrion AZ, Van Lint C, Herbein G, Aggarwal BB: Exogenous Nef protein activates NF-kappa B, AP-1, and c-Jun N-terminal kinase and stimulates HIV transcription in promonocytic cells. Role in AIDS pathogenesis. J Biol Chem 2003, 278(4):2219-2227.
• [70]Champion S, Sauzet C, Bremond P, Benbrahim K, Abraldes J, Seree E, Barra Y, Villard PH: Activation of the NF kappa B pathway enhances AhR expression in intestinal caco-2 cells. ISRN Toxicol 2013, 2013:792452.
• [71]Gladiator A, Wangler N, Trautwein-Weidner K, LeibundGut-Landmann S: Cutting edge: IL-17-secreting innate lymphoid cells are essential for host defense against fungal infection. J Immunol 2013, 190(2):521-525.
• [72]Witowski J, Pawlaczyk K, Breborowicz A, Scheuren A, Kuzlan-Pawlaczyk M, Wisniewska J, Polubinska A, Friess H, Gahl GM, Frei U, Jörres A: IL-17 stimulates intraperitoneal neutrophil infiltration through the release of GRO alpha chemokine from mesothelial cells. J Immunol 2000, 165(10):5814-5821.
• [73]Markel G, Bar-Haim E, Zahavy E, Cohen H, Cohen O, Shafferman A, Velan B: The involvement of IL-17A in the murine response to sub-lethal inhalational infection with Francisella tularensis. PLoS One 2010, 5(6):e11176.
• [74]Wondimu Z, Santodomingo-Garzon T, Le T, Swain MG: Protective role of interleukin-17 in murine NKT cell-driven acute experimental hepatitis. Am J Pathol 2010, 177(5):2334-2346.
• [75]Mellett M, Atzei P, Horgan A, Hams E, Floss T, Wurst W, Fallon PG, Moynagh PN: Orphan receptor IL-17RD tunes IL-17A signalling and is required for neutrophilia. Nat Commun 2012, 3:1119.
• [76]Eyerich K, Foerster S, Rombold S, Seidl HP, Behrendt H, Hofmann H, Ring J, Traidl-Hoffmann C: Patients with chronic mucocutaneous candidiasis exhibit reduced production of Th17-associated cytokines IL-17 and IL-22. J Invest Dermatol 2008, 128(11):2640-2645.
• [77]Steubesand N, Kiehne K, Brunke G, Pahl R, Reiss K, Herzig KH, Schubert S, Schreiber S, Folsch UR, Rosenstiel P, Arlt A: The expression of the beta-defensins hBD-2 and hBD-3 is differentially regulated by NF-kappaB and MAPK/AP-1 pathways in an in vitro model of Candida esophagitis. BMC Immunol 2009, 10:36. BioMed Central Full Text
• [78]Urban CF, Ermert D, Schmid M, Abu-Abed U, Goosmann C, Nacken W, Brinkmann V, Jungblut PR, Zychlinsky A: Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans. PLoS Pathog 2009, 5(10):e1000639.
• [79]Kleinegger CL, Stoeckel DC, Kurago ZB: A comparison of salivary calprotectin levels in subjects with and without oral candidiasis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001, 92(1):62-67.
• [80]Sweet SP, Denbury AN, Challacombe SJ: Salivary calprotectin levels are raised in patients with oral candidiasis or Sjogren’s syndrome but decreased by HIV infection. Oral Microbiol Immunol 2001, 16(2):119-123.
• [81]Lacasse M, Fortier C, Trudel L, Collet AJ, Deslauriers N: Experimental oral candidosis in the mouse: microbiologic and histologic aspects. J Oral Pathol Med 1990, 19(3):136-141.
• [82]Feller L, Khammissa RA, Chandran R, Altini M, Lemmer J: Oral candidosis in relation to oral immunity. J Oral Pathol Med 2013, 43(8):563-569.
• [83]Marquis M, Lewandowski D, Dugas V, Aumont F, Senechal S, Jolicoeur P, Hanna Z, de Repentigny L: CD8+ T cells but not polymorphonuclear leukocytes are required to limit chronic oral carriage of Candida albicans in transgenic mice expressing human immunodeficiency virus type 1. Infect Immun 2006, 74(4):2382-2391.
• [84]Li H, Reeves RK: Functional perturbation of classical natural killer and innate lymphoid cells in the oral mucosa during SIV infection. Front Immunol 2012, 3:417.
• [85]Xu H, Wang X, Liu DX, Moroney-Rasmussen T, Lackner AA, Veazey RS: IL-17-producing innate lymphoid cells are restricted to mucosal tissues and are depleted in SIV-infected macaques. Mucosal Immunol 2012, 5(6):658-669.
• [86]Poudrier J, Weng X, Kay DG, Pare G, Calvo EL, Hanna Z, Kosco-Vilbois MH, Jolicoeur P: The AIDS disease of CD4C/HIV transgenic mice shows impaired germinal centers and autoantibodies and develops in the absence of IFN-gamma and IL-6. Immunity 2001, 15(2):173-185.
• [87]Priceputu E, Rodrigue I, Chrobak P, Poudrier J, Mak TW, Hanna Z, Hu C, Kay DG, Jolicoeur P: The Nef-mediated AIDS-like disease of CD4C/human immunodeficiency virus transgenic mice is associated with increased Fas/FasL expression on T cells and T-cell death but is not prevented in Fas-, FasL-, tumor necrosis factor receptor 1-, or interleukin-1beta-converting enzyme-deficient or Bcl2-expressing transgenic mice. J Virol 2005, 79(10):6377-6391.
• [88]Kay DG, Yue P, Hanna Z, Jothy S, Tremblay E, Jolicoeur P: Cardiac disease in transgenic mice expressing human immunodeficiency virus-1 nef in cells of the immune system. Am J Pathol 2002, 161(1):321-335.
• [89]Jin W, Zhou XF, Yu J, Cheng X, Sun SC: Regulation of Th17 cell differentiation and EAE induction by MAP3K NIK. Blood 2009, 113(26):6603-6610.