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Arginase 1 expression by macrophages promotes Cryptococcus neoformans proliferation and invasion into brain microvascular endothelial cells.

ABSTRACT: Cryptococcal meningoencephalitis caused by C. neoformans infection is the most common cause of death in HIV/AIDS patients. Macrophages are recognized as key players in promoting the growth, proliferation, and dissemination of Cryptococcus. However, macrophage-derived factors that underlie these pathogenic responses remain unclear. Thus, the aim of this study is to investigate the permissive factors of macrophages that support the pathogenicity of Cryptococcus infection. We generated mRNA expression profiles of alveolar macrophage isolated from BALB/c mice intranasally treated with PBS or infected with C. neoformans H99 at 7 and 14 days postinfection and performed a comparative transcriptomic analysis to investigate the transcriptomic changes of macrophages during infection. Alveolar macrophages isolated from C. neoformans-infected mice showed dynamic gene expression patterns which were altered from a protective M1-like cells to a pathogenic M2-like phenotype. Interestingly, Arg1, encoded for enzyme arginase-1, was a predominant up-regulated gene observed in alveolar macrophages after infection at 14 days and the activation of macrophage arginase activity is required for the development of M2 macrophages that supports cryptococcal growth, proliferation, and dissemination.

ORGANISM(S): Mus musculus

PROVIDER: GSE214001 | GEO | 2022/11/30

REPOSITORIES: GEO

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