Candida albicans Morphology and Dendritic Cell Subsets Determine T Helper Cell Differentiation

Sakeen W Kashem, Botond Z Igyártó, Maryam Gerami-Nejad, Yosuke Kumamoto, Javed Mohammed, Elizabeth Jarrett, Rebecca A Drummond, Sandra M Zurawski, Gerard Zurawski, Judith Berman, Akiko Iwasaki, Gordon D Brown, Daniel H Kaplan

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98 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)356-366
Number of pages11
JournalImmunity
Volume42
Issue number2
Early online date10 Feb 2015
DOIs
Publication statusPublished - 17 Feb 2015

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Keywords

  • Candida Albicans
  • Morphology
  • Dendritic Cell
  • T Helper Cell Differntiation

Cite this

Kashem, S. W., Igyártó, B. Z., Gerami-Nejad, M., Kumamoto, Y., Mohammed, J., Jarrett, E., ... Kaplan, D. H. (2015). Candida albicans Morphology and Dendritic Cell Subsets Determine T Helper Cell Differentiation. Immunity, 42(2), 356-366. https://doi.org/10.1016/j.immuni.2015.01.008