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 language | English |
|---|---|
| Pages (from-to) | 356-366 |
| Number of pages | 11 |
| Journal | Immunity |
| Volume | 42 |
| Issue number | 2 |
| Early online date | 10 Feb 2015 |
| DOIs | |
| Publication status | Published - 17 Feb 2015 |
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Keywords
- Candida Albicans
- Morphology
- Dendritic Cell
- T Helper Cell Differntiation
Cite this
Candida albicans Morphology and Dendritic Cell Subsets Determine T Helper Cell Differentiation. / Kashem, Sakeen W; Igyártó, Botond Z; Gerami-Nejad, Maryam; Kumamoto, Yosuke; Mohammed, Javed; Jarrett, Elizabeth; Drummond, Rebecca A; Zurawski, Sandra M; Zurawski, Gerard; Berman, Judith; Iwasaki, Akiko; Brown, Gordon D; Kaplan, Daniel H.
In: Immunity, Vol. 42, No. 2, 17.02.2015, p. 356-366.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Candida albicans Morphology and Dendritic Cell Subsets Determine T Helper Cell Differentiation
AU - Kashem, Sakeen W
AU - Igyártó, Botond Z
AU - Gerami-Nejad, Maryam
AU - Kumamoto, Yosuke
AU - Mohammed, Javed
AU - Jarrett, Elizabeth
AU - Drummond, Rebecca A
AU - Zurawski, Sandra M
AU - Zurawski, Gerard
AU - Berman, Judith
AU - Iwasaki, Akiko
AU - Brown, Gordon D
AU - Kaplan, Daniel H
N1 - Copyright © 2015 Elsevier Inc. All rights reserved. Acknowledgements 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.
PY - 2015/2/17
Y1 - 2015/2/17
N2 - 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.
AB - 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.
KW - Candida Albicans
KW - Morphology
KW - Dendritic Cell
KW - T Helper Cell Differntiation
U2 - 10.1016/j.immuni.2015.01.008
DO - 10.1016/j.immuni.2015.01.008
M3 - Article
VL - 42
SP - 356
EP - 366
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 2
ER -