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Cell host & microbe

Cell host & microbe

IF: 18.7
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A human commensal-pathogenic fungus suppresses host immunity via targeting TBK1

Published:30 July 2024 DOI:

Abstract

Candida albicans stably colonizes humans but is the leading cause of hospital-acquired fungemia. Traditionally, masking immunogenic moieties has been viewed as a tactic for immune evasion. Here, we demonstrate that C.?albicans blocks type I interferon (IFN-I) signaling via translocating an effector protein Cmi1 into host cells. Mechanistically, Cmi1 binds and inhibits TANK-binding kinase 1 (TBK1) to abrogate IFN-regulatory factor 3 (IRF3) phosphorylation, thereby suppressing the IFN-I cascade. Murine infection with a cmi1 mutant displays an exaggerated IFN-I response in both kidneys and bone-marrow-derived macrophages, leading to rapid fungal clearance and host survival. Remarkably, the lack of CMI1 compromises gut commensalism and increases IFN-I response in mouse colonic cells. These phenotypes of cmi1 are rescued by the depletion of IFN-I receptor. This work establishes the importance of TBK1 inhibition in fungal pathogenesis and reveals that a human commensal-pathogenic fungus significantly impacts host immunity during gut colonization and infection via delivering effector proteins into host cells.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
GSK8612 2361659-62-1 C17H17BrF3N7O2S 69 suppliers Inquiry
GSK8612 2361659-62-1 C17H17BrF3N7O2S 69 suppliers Inquiry
GSK8612 2361659-62-1 C17H17BrF3N7O2S 69 suppliers Inquiry
GSK8612 2361659-62-1 C17H17BrF3N7O2S 69 suppliers Inquiry

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