Type I IFN Induction via Poly-ICLC Protects Mice against Cryptococcosis

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Meningoencephalitis due to Cryptococcus neoformans is the leading cause of mortality in AIDS patients in the developing world. It has been known that depletion of CD4 T cells is the most critical predisposing factor to cryptococcosis in HIV infected patients. What has not been clear is the effect of HIV-induced innate inflammation in susceptibility to cryptococcosis. We treated C. neoformans infected mice with poly-ICLC (pICLC), a dsRNA virus mimic, to study the role of virus-induced type I IFN in host defense against cryptococcosis. PICLC treatment induced type I IFN in C. neoformans infected mice via MDA5 and significantly prolonged the survival of mice with reduced fungal burden in the brain. PICLC also protected mice from cryptococcosis caused by C. gattii. PICLC treatment recruited large numbers of neutrophils and Ly6Chigh monocytes into the lung parenchyma and suppressed eosinophilia. PICLC-mediated protection against C. neoformans required CD4 T cells and was associated with suppressed Th2 and enhanced Th17 responses. IFNγ and IL-17A were also important for pICLC-induced protection of infected mice. Our study demonstrates that induction of type I IFN dramatically improves host resistance against cryptococci by beneficial alterations in both innate and adaptive immune responses as long as CD4 cells are not depleted.

Vyšlo v časopise: Type I IFN Induction via Poly-ICLC Protects Mice against Cryptococcosis. PLoS Pathog 11(8): e32767. doi:10.1371/journal.ppat.1005040
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005040

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