期刊
出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2020484118
关键词
macrophages; fungal hyphae; mechanical force; podosomes; cytoskeleton
资金
- UK Medical Research Council [MR/M026663/1, MR/M026663/2]
- University of Aberdeen
- Wellcome [097377, 101873, 200208, 102705]
- Medical Research Council Centre for Medical Mycology [MR/N006364/1, MR/N006364/2]
- European Research Council Advanced Grant [833247]
- Spinoza Grant of the Netherlands Organization for Scientific Research
- Microscopy and Histology Core Facility at the University of Aberdeen
- MRC [MR/N006364/1] Funding Source: UKRI
Innate immunity is vital in protecting against fungal infections, but pathogens have evolved ways to evade immune cells. Researchers found that macrophages can counteract pathogen evasion by folding fungal hyphae, promoting successful fungal clearance through engulfment and inhibition of hyphal growth.
Innate immunity provides essential protection against life-threatening fungal infections. However, the outcomes of individual skirmishes between immune cells and fungal pathogens are not a foregone conclusion because some pathogens have evolved mechanisms to evade phagocytic recognition, engulfment, and killing. For example, Candida albicans can escape phagocytosis by activating cellular morphogenesis to form lengthy hyphae that are challenging to engulf. Through live imaging of C. albicans-macrophage interactions, we discovered that macrophages can counteract this by folding fungal hyphae. The folding of fungal hyphae is promoted by Dectin-1, beta 2-integrin, VASP, actin-myosin polymerization, and cell motility. Folding facilitates the complete engulfment of long hyphae in some cases and it inhibits hyphal growth, presumably tipping the balance toward successful fungal clearance.
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