Myeloid Derived Hypoxia Inducible Factor 1-alpha Is Required for Protection against Pulmonary Infection

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Due to the limited treatment options and severity of invasive fungal infections, a better understanding of fungal-host interactions is needed for the development of new therapies. Recent studies have implicated a role for hypoxia inducible factor 1-alpha (HIF1α) in the regulation of inflammation and host defense responses to microbial pathogens. In this study, we discover that HIF1α is required for protection and murine survival to Aspergillus fumigatus pulmonary challenge. First, we observed that nuclear HIF1α protein levels are reduced in the murine corticosteroid immunosuppressed model of invasive pulmonary aspergillosis, suggesting its involvement in disease outcome. We then tested the hypothesis that HIF1α is required by innate immune effector cells to control/prevent A. fumigatus growth and invasion. Surprisingly, we observed that the role of myeloid HIF1α is not to mediate innate effector cell A. fumigatus killing directly, but rather to induce and maintain a protective immune response that ensures proper effector cell recruitment and survival at the site of infection. These findings provide a better understanding of host mechanisms involved in thwarting fungal pathogenesis, have implications for host susceptibility, and reveal the potential for novel treatment strategies involving HIF1α mediated signaling in the lung in immune suppressed patients.

Vyšlo v časopise: Myeloid Derived Hypoxia Inducible Factor 1-alpha Is Required for Protection against Pulmonary Infection. PLoS Pathog 10(9): e32767. doi:10.1371/journal.ppat.1004378
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004378

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