In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 1 ( 2021-1-20), p. e1009221-
Abstract:
During oropharyngeal candidiasis (OPC), Candida albicans invades and damages oral epithelial cells, which respond by producing proinflammatory mediators that recruit phagocytes to foci of infection. The ephrin type-A receptor 2 (EphA2) detects β-glucan and plays a central role in stimulating epithelial cells to release proinflammatory mediators during OPC. The epidermal growth factor receptor (EGFR) also interacts with C . albicans and is known to be activated by the Als3 adhesin/invasin and the candidalysin pore-forming toxin. Here, we investigated the interactions among EphA2, EGFR, Als3 and candidalysin during OPC. We found that EGFR and EphA2 constitutively associate with each other as part of a heteromeric physical complex and are mutually dependent for C . albicans- induced activation. Als3-mediated endocytosis of a C . albicans hypha leads to the formation of an endocytic vacuole where candidalysin accumulates at high concentration. Thus, Als3 potentiates targeting of candidalysin, and both Als3 and candidalysin are required for C . albicans to cause maximal damage to oral epithelial cells, sustain activation of EphA2 and EGFR, and stimulate pro-inflammatory cytokine and chemokine secretion. In the mouse model of OPC, C . albicans- induced production of CXCL1/KC and CCL20 is dependent on the presence of candidalysin and EGFR, but independent of Als3. The production of IL-1α and IL-17A also requires candidalysin but is independent of Als3 and EGFR. The production of TNFα requires Als1, Als3, and candidalysin. Collectively, these results delineate the complex interplay among host cell receptors EphA2 and EGFR and C . albicans virulence factors Als1, Als3 and candidalysin during the induction of OPC and the resulting oral inflammatory response.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009221
DOI:
10.1371/journal.ppat.1009221.g001
DOI:
10.1371/journal.ppat.1009221.g002
DOI:
10.1371/journal.ppat.1009221.g003
DOI:
10.1371/journal.ppat.1009221.g004
DOI:
10.1371/journal.ppat.1009221.g005
DOI:
10.1371/journal.ppat.1009221.g006
DOI:
10.1371/journal.ppat.1009221.g007
DOI:
10.1371/journal.ppat.1009221.g008
DOI:
10.1371/journal.ppat.1009221.g009
DOI:
10.1371/journal.ppat.1009221.g010
DOI:
10.1371/journal.ppat.1009221.s001
DOI:
10.1371/journal.ppat.1009221.s002
DOI:
10.1371/journal.ppat.1009221.s003
DOI:
10.1371/journal.ppat.1009221.s004
DOI:
10.1371/journal.ppat.1009221.s005
DOI:
10.1371/journal.ppat.1009221.s006
DOI:
10.1371/journal.ppat.1009221.s007
DOI:
10.1371/journal.ppat.1009221.s008
DOI:
10.1371/journal.ppat.1009221.s009
DOI:
10.1371/journal.ppat.1009221.s010
DOI:
10.1371/journal.ppat.1009221.s011
DOI:
10.1371/journal.ppat.1009221.s012
DOI:
10.1371/journal.ppat.1009221.s013
DOI:
10.1371/journal.ppat.1009221.s014
DOI:
10.1371/journal.ppat.1009221.s015
DOI:
10.1371/journal.ppat.1009221.s016
DOI:
10.1371/journal.ppat.1009221.s017
DOI:
10.1371/journal.ppat.1009221.s018
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
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