Candida albicans elicits protective allergic responses via platelet mediated T helper 2 and T helper 17 cell polarization.
Candida
Dkk-1
GP1bα
allergy
asthma
candidalysin
platelets
Journal
Immunity
ISSN: 1097-4180
Titre abrégé: Immunity
Pays: United States
ID NLM: 9432918
Informations de publication
Date de publication:
09 11 2021
09 11 2021
Historique:
received:
25
01
2021
revised:
19
05
2021
accepted:
10
08
2021
pubmed:
11
9
2021
medline:
15
12
2021
entrez:
10
9
2021
Statut:
ppublish
Résumé
Fungal airway infection (airway mycosis) is an important cause of allergic airway diseases such as asthma, but the mechanisms by which fungi trigger asthmatic reactions are poorly understood. Here, we leverage wild-type and mutant Candida albicans to determine how this common fungus elicits characteristic Th2 and Th17 cell-dependent allergic airway disease in mice. We demonstrate that rather than proteinases that are essential virulence factors for molds, C. albicans instead promoted allergic airway disease through the peptide toxin candidalysin. Candidalysin activated platelets through the Von Willebrand factor (VWF) receptor GP1bα to release the Wnt antagonist Dickkopf-1 (Dkk-1) to drive Th2 and Th17 cell responses that correlated with reduced lung fungal burdens. Platelets simultaneously precluded lethal pulmonary hemorrhage resulting from fungal lung invasion. Thus, in addition to hemostasis, platelets promoted protection against C. albicans airway mycosis through an antifungal pathway involving candidalysin, GP1bα, and Dkk-1 that promotes Th2 and Th17 responses.
Identifiants
pubmed: 34506733
pii: S1074-7613(21)00339-3
doi: 10.1016/j.immuni.2021.08.009
pmc: PMC8585696
mid: NIHMS1734500
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
2595-2610.e7Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL140398
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR024574
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIDCR NIH HHS
ID : R37 DE022550
Pays : United States
Organisme : BLRD VA
ID : I01 BX004828
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA125123
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI053831
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL117181
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI135803
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests D.B.C is a scientific consultant to Atrapos Therapeutics, LLC and Pulmocide, LLC.
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