title: 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.
abstract: 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.
authors.affiliation: Department of Microbiology, Infectious Diseases and Immunology, Faculty of Medicine, University of Montreal, C.P. 6128, succursale Centre-Ville, Montreal, Quebec, H3C 3J7, Canada. mathieu.goupil@umontreal.ca.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Goupil
authors.affiliation: Department of Microbiology, Infectious Diseases and Immunology, Faculty of Medicine, University of Montreal, C.P. 6128, succursale Centre-Ville, Montreal, Quebec, H3C 3J7, Canada. vincent.cousineau-cote@umontreal.ca.
authors.forename: Vincent
authors.initials: V
authors.lastname: Cousineau-Côté
authors.affiliation: Department of Microbiology, Infectious Diseases and Immunology, Faculty of Medicine, University of Montreal, C.P. 6128, succursale Centre-Ville, Montreal, Quebec, H3C 3J7, Canada. francine.aumont@umontreal.ca.
authors.forename: Francine
authors.initials: F
authors.lastname: Aumont
authors.affiliation: Department of Microbiology, Infectious Diseases and Immunology, Faculty of Medicine, University of Montreal, C.P. 6128, succursale Centre-Ville, Montreal, Quebec, H3C 3J7, Canada. serge.senechal@umontreal.ca.
authors.forename: Serge
authors.initials: S
authors.lastname: Sénéchal
authors.affiliation: Pathology and Cell Biology, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada. louis.gaboury@umontreal.ca.|Histology and Molecular Pathology research unit, Institute for Research in Immunology and Cancer, C.P. 6128, succursale Centre-Ville, Montreal, QC, H3C 3J7, Canada. louis.gaboury@umontreal.ca.
authors.forename: Louis
authors.initials: L
authors.lastname: Gaboury
authors.affiliation: Medicine, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada. zaher.hanna@ircm.qc.ca.|Laboratory of Molecular Biology, Clinical Research Institute of Montreal, Montreal, Quebec, Canada. zaher.hanna@ircm.qc.ca.|Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada. zaher.hanna@ircm.qc.ca.
authors.forename: Zaher
authors.initials: Z
authors.lastname: Hanna
authors.affiliation: Department of Microbiology, Infectious Diseases and Immunology, Faculty of Medicine, University of Montreal, C.P. 6128, succursale Centre-Ville, Montreal, Quebec, H3C 3J7, Canada. paul.jolicoeur@ircm.qc.ca.|Laboratory of Molecular Biology, Clinical Research Institute of Montreal, Montreal, Quebec, Canada. paul.jolicoeur@ircm.qc.ca.|Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada. paul.jolicoeur@ircm.qc.ca.
authors.forename: Paul
authors.initials: P
authors.lastname: Jolicoeur
authors.affiliation: Department of Microbiology, Infectious Diseases and Immunology, Faculty of Medicine, University of Montreal, C.P. 6128, succursale Centre-Ville, Montreal, Quebec, H3C 3J7, Canada. louis.de.repentigny@umontreal.ca.
authors.forename: Louis
authors.initials: L
authors.lastname: de Repentigny
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002176:Candida albicans / Q000276:immunology*; D002180:Candidiasis, Oral / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D019076:Transgenes / Q000276:immunology; D000097043:Interleukin-22
chemical_list: D020381:Interleukin-17; D007378:Interleukins; D000097043:Interleukin-22