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Cell Rep ; 36(8): 109584, 2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34433036

RESUMO

Evasion of killing by immune cells is crucial for fungal survival in the host. For the human fungal pathogen Candida albicans, internalization by macrophages induces a transition from yeast to filaments that promotes macrophage death and fungal escape. Nutrient deprivation, alkaline pH, and oxidative stress have been implicated as triggers of intraphagosomal filamentation; however, the impact of other host-derived factors remained unknown. Here, we show that lysates prepared from macrophage-like cell lines and primary macrophages robustly induce C. albicans filamentation. Enzymatic treatment of lysate implicates a phosphorylated protein, and bioactivity-guided fractionation coupled to mass spectrometry identifies the immunomodulatory phosphoprotein PTMA as a candidate trigger of C. albicans filamentation. Immunoneutralization of PTMA within lysate abolishes its activity, strongly supporting PTMA as a filament-inducing component of macrophage lysate. Adding to the known repertoire of physical factors, this work implicates a host protein in the induction of C. albicans filamentation within immune cells.


Assuntos
Proteínas Fúngicas/imunologia , Hifas/patogenicidade , Macrófagos/imunologia , Fagossomos/microbiologia , Candida albicans/metabolismo , Candida albicans/patogenicidade , Linhagem Celular , Proteínas Fúngicas/metabolismo , Humanos , Hifas/metabolismo , Evasão da Resposta Imune/imunologia
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