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

Research output: Contribution to journalArticlepeer-review

106 Scopus citations

Abstract

Candida albicans is a dimorphic fungus responsible for chronic mucocutaneous and systemic infections.Mucocutaneous immunity to C.albicans requires Thelper 17 (Th17) cell differentiation that is thought to depend on recognition of filamentous C.albicans. Systemic immunity is considered Tcell 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 providedprotection 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 (US)
Pages (from-to)356-366
Number of pages11
JournalImmunity
Volume42
Issue number2
DOIs
StatePublished - Feb 17 2015

Bibliographical note

Funding Information:
We thank M. Jenkins for assistance with 2W1S tetramers. B. Chicoine provided technical assistance. We thank Bruce Klein and Marcel Wuethrich for assistance with celc7a −/− mice. We also thank the University of Minnesota Research Animal Resources staff for expert animal care and P. Champoux and T. Martin of the Flow Cytometry Core Facility at the Center for Immunology for assistance with flow cytometry experiments. This work was supported by grants from the NIH (AR056632 and AR060744) to D.H.K., a Dermatology Foundation research award (B.Z.I.), and an American Skin Association research award (B.Z.I.). D.H.K. is also supported by the Al Zelickson Family endowed professorship. S.W.K. was supported by the University of Minnesota NIH MSTP grant T32 GM008244.

Publisher Copyright:
© 2015 Elsevier Inc.

Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.

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