title: Candida albicans morphology and dendritic cell subsets determine T helper cell differentiation.
abstract: Candida albicans is a dimorphic fungus responsible for chronic mucocutaneous and systemic infections. Mucocutaneous immunity to C. albicans requires T helper 17 (Th17) cell differentiation that is thought to depend on recognition of filamentous C. albicans. Systemic immunity is considered T cell independent. Using a murine skin infection model, we compared T helper cell responses to yeast and filamentous C. albicans. We found that only yeast induced Th17 cell responses through a mechanism that required Dectin-1-mediated expression of interleukin-6 (IL-6) by Langerhans cells. Filamentous forms induced Th1 without Th17 cell responses due to the absence of Dectin-1 ligation. Notably, Th17 cell responses provided protection against cutaneous infection while Th1 cell responses provided protection against systemic infection. Thus, C. albicans morphology drives distinct T helper cell responses that provide tissue-specific protection. These findings provide insight into compartmentalization of Th cell responses and C. albicans pathogenesis and have critical implications for vaccine strategies.
authors: Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
authors: Sakeen W
authors: SW
authors: Kashem
authors: Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
authors: Botond Z
authors: BZ
authors: Igyarto
authors: Department of Molecular and Cellular Biology, University of Minnesota, Minneapolis, MN 55455, USA.
authors: Maryam
authors: M
authors: Gerami-Nejad
authors: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors: Yosuke
authors: Y
authors: Kumamoto
authors: Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
authors: Javed A
authors: JA
authors: Mohammed
authors: Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
authors: Elizabeth
authors: E
authors: Jarrett
authors: Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, UK.
authors: Rebecca A
authors: RA
authors: Drummond
authors: Baylor Institute for Immunology Research and INSERM U899 - ANRS Center for Human Vaccines, 3434 Live Oak Street, Dallas, TX 75204.
authors: Sandra M
authors: SM
authors: Zurawski
authors: Baylor Institute for Immunology Research and INSERM U899 - ANRS Center for Human Vaccines, 3434 Live Oak Street, Dallas, TX 75204.
authors: Gerard
authors: G
authors: Zurawski
authors: Department of Molecular and Cellular Biology, University of Minnesota, Minneapolis, MN 55455, USA.|Department of Molecular Microbiology and Biotechnology, George Wise Faculty of Life Sciences Tel Aviv University, Ramat Aviv, 69978 Israel.
authors: Judith
authors: J
authors: Berman
authors: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors: Akiko
authors: A
authors: Iwasaki
authors: Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, UK.
authors: Gordon D
authors: GD
authors: Brown
authors: Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
authors: Daniel H
authors: DH
authors: Kaplan
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics; D002176:Candida albicans / Q000276:immunology; D002178:Candidiasis, Chronic Mucocutaneous / Q000276:immunology* / Q000382:microbiology; D002454:Cell Differentiation / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D007801:Langerhans Cells / Q000276:immunology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012097:Repressor Proteins / Q000235:genetics; D012867:Skin / Q000276:immunology / Q000382:microbiology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D058504:Th17 Cells / Q000166:cytology* / Q000276:immunology*; D000099181:Dectin-1
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D015850:Interleukin-6; D037181:Lectins, C-Type; D012097:Repressor Proteins; D000099181:Dectin-1; C533289:SNFT protein, mouse