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

被引:191
作者
Kashem, Sakeen W. [1 ]
Igyarto, Botond Z. [1 ]
Gerami-Nejad, Maryam [2 ]
Kumamoto, Yosuke [3 ]
Mohammed, Javed [1 ]
Jarrett, Elizabeth [1 ]
Drummond, Rebecca A. [4 ]
Zurawski, Sandra M. [5 ,6 ]
Zurawski, Gerard [5 ,6 ]
Berman, Judith [2 ,7 ]
Iwasaki, Akiko [3 ]
Brown, Gordon D. [4 ]
Kaplan, Daniel H. [1 ]
机构
[1] Univ Minnesota, Dept Dermatol, Ctr Immunol, Minneapolis, MN 55455 USA
[2] Univ Minnesota, Dept Mol & Cellular Biol, Minneapolis, MN 55455 USA
[3] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
[4] Univ Aberdeen, Inst Med Sci, Aberdeen Fungal Grp, Aberdeen AB25 2ZD, Scotland
[5] Baylor Inst Immunol Res, Dallas, TX 75204 USA
[6] ANRS Ctr Human Vaccines, INSERM, U899, Dallas, TX 75204 USA
[7] Tel Aviv Univ, George Wise Fac Life Sci, Dept Mol Microbiol & Biotechnol, IL-69978 Ramat Aviv, Israel
关键词
CHRONIC MUCOCUTANEOUS CANDIDIASIS; CYTOKINE PRODUCTION; T(H)17 CELLS; IN-VITRO; DECTIN-1; RESPONSES; IMMUNE; IL-17; INDUCTION; GAMMA;
D O I
10.1016/j.immuni.2015.01.008
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:356 / 366
页数:11
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