Hypoxia inducible factors (HIFs) are the known transcription factors adapting cells to low levels of oxygen tension (hypoxia). In addition, HIFs also drive gene expression after inflammatory stimulation in monocytes and macrophages.

In our experiments we analyzed bone marrow derived dendritic cells (BmDC) from mice expressing or lacking functional HIF-1α protein in cells of the myeloid lineage after stimulation with synthetic TLR ligands. Whereas the bacterial stimuli LPS (lipopolysaccharides) and CpG-ODN induced HIF-1α protein and mRNA levels, viral Poly(I:C) did not. Furthermore, we could detect a significant induction of the HIF-1 target genes VEGF (vascular endothelial growth factor) and A2B adenosine receptor after stimulation with LPS or CpG-ODN.

Because dendritic cells produce type I interferons as a very rapid answer after an inflammatory challenge we analyzed expression of these cytokines in BmDC expressing or lacking functional HIF-1α. We found that expression of functional HIF-1α is indispensable for the inflammatory induction of IFNα subtypes 4 and 12 mRNA. Furthermore, HIF-1α lacking BmDC secreted significantly less IFN-β and failed to properly activate cytotoxic T cells. These data implicate a new and critical role for the transcription factor HIF-1 at the crosslink between innate and adaptive immune response.