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Immunity. 2015 Feb 17;42(2):356-366. doi: 10.1016/j.immuni.2015.01.008. Epub 2015 Feb 10.

Candida albicans morphology and dendritic cell subsets determine T helper cell differentiation.

Author information

1
Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
2
Department of Molecular and Cellular Biology, University of Minnesota, Minneapolis, MN 55455, USA.
3
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
4
Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, UK.
5
Baylor Institute for Immunology Research and INSERM U899 - ANRS Center for Human Vaccines, 3434 Live Oak Street, Dallas, TX 75204.
6
Department of Molecular Microbiology and Biotechnology, George Wise Faculty of Life Sciences Tel Aviv University, Ramat Aviv, 69978 Israel.
#
Contributed equally

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.

PMID:
25680275
PMCID:
PMC4343045
DOI:
10.1016/j.immuni.2015.01.008
[Indexed for MEDLINE]
Free PMC Article

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