Hypoxia-inducible factor 1α modulates metabolic activity and cytokine release in anti-Aspergillus fumigatus immune responses initiated by human dendritic cells.

This study investigated the functional relevance of HIF-1α in the anti-A. fumigatus immune response initiated by human DCs. Hypoxic cell culture conditions were included because hypoxic microenvironments occur during A. fumigatus infections and may influence the host immune response. HIF-1α was stabilized in DCs following stimulation with A. fumigatus under normoxic and hypoxic conditions. This stabilization was partially dependent on dectin-1, the major receptor for A. fumigatus on human DCs. Using siRNA-based HIF-1α silencing combined with genome-wide transcriptional analysis, a modulatory effect of HIF-1α on the anti-fungal immune response of human DCs was identified. Specifically, the difference in the transcriptomes of HIF-1α silenced and non-silenced DCs indicated that HIF-1α contributes to DC metabolism and cytokine release in response to A. fumigatus under normoxic as well as hypoxic conditions. This was confirmed by further down-stream analyses that included metabolite analysis and cytokine profiling of a time-course infection experiment. Thereby, this study revealed a so far undescribed functional relevance of HIF-1α in human DC responses against A. fumigatus. PMID: 26387061 [PubMed - as supplied by publisher]
Source: International Journal of Medical Microbiology - Category: Microbiology Authors: Tags: Int J Med Microbiol Source Type: research