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

doi:10.1016/j.immuni.2015.01.008

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 journal › Article › peer-review

115 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 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	https://doi.org/10.1016/j.immuni.2015.01.008
Publication status	Published - 17 Feb 2015

Keywords

Candida Albicans
Morphology
Dendritic Cell
T Helper Cell Differntiation

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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 › peer-review

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. / Candida albicans Morphology and Dendritic Cell Subsets Determine T Helper Cell Differentiation. In: Immunity. 2015 ; Vol. 42, No. 2. pp. 356-366.

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title = "Candida albicans Morphology and Dendritic Cell Subsets Determine T Helper Cell Differentiation",

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.",

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author = "Kashem, {Sakeen W} and Igy{\'a}rt{\'o}, {Botond Z} and Maryam Gerami-Nejad and Yosuke Kumamoto and Javed Mohammed and Elizabeth Jarrett and Drummond, {Rebecca A} and Zurawski, {Sandra M} and Gerard Zurawski and Judith Berman and Akiko Iwasaki and Brown, {Gordon D} and Kaplan, {Daniel H}",

note = "Copyright {\textcopyright} 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.",

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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.

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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.

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