Oral epithelial cells orchestrate innate type 17 responses to Candida albicans through the virulence factor candidalysin
is a dimorphic commensal fungus that causes severe oral infections in immunodeficient patients. Invasion of hyphae into oral epithelium is an essential virulence trait. Interleukin-17 (IL-17) signaling is required for both innate and adaptive immunity to During the innate response, IL-17 is produced...
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Published in | Science immunology Vol. 2; no. 17 |
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Main Authors | , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
03.11.2017
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Subjects | |
Online Access | Get more information |
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Summary: | is a dimorphic commensal fungus that causes severe oral infections in immunodeficient patients. Invasion of
hyphae into oral epithelium is an essential virulence trait. Interleukin-17 (IL-17) signaling is required for both innate and adaptive immunity to
During the innate response, IL-17 is produced by γδ T cells and a poorly understood population of innate-acting CD4
αβ T cell receptor (TCRαβ)
cells, but only the TCRαβ
cells expand during acute infection. Confirming the innate nature of these cells, the TCR was not detectably activated during the primary response, as evidenced by
mice that report antigen-specific signaling through the TCR. Rather, the expansion of innate TCRαβ
cells was driven by both intrinsic and extrinsic IL-1R signaling. Unexpectedly, there was no requirement for CCR6/CCL20-dependent recruitment or prototypical fungal pattern recognition receptors. However,
mutants that cannot switch from yeast to hyphae showed impaired TCRαβ
cell proliferation and
expression. This prompted us to assess the role of candidalysin, a hyphal-associated peptide that damages oral epithelial cells and triggers production of inflammatory cytokines including IL-1. Candidalysin-deficient strains failed to up-regulate
or drive the proliferation of innate TCRαβ
cells. Moreover, candidalysin signaled synergistically with IL-17, which further augmented the expression of IL-1α/β and other cytokines. Thus, IL-17 and
, via secreted candidalysin, amplify inflammation in a self-reinforcing feed-forward loop. These findings challenge the paradigm that hyphal formation per se is required for the oral innate response and demonstrate that establishment of IL-1- and IL-17-dependent innate immunity is induced by tissue-damaging hyphae. |
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ISSN: | 2470-9468 |
DOI: | 10.1126/sciimmunol.aam8834 |