Modulation of Innate Immunity by Hypoxia

Low oxygen tension occurs virtually in every site of inflammation, necrotic foci, infection, and wounding. It has become widely recognized that the dynamic interaction between multiple cellular components of damaged tissues, including but not limited to immune and stromal inflammatory cells, and microenvironmental factors, for example, hypoxia, plays a critical role in the pathophysiology of human diseases ranging from infections to chronic inflammation to cancer. Hypoxia modulates leukocyte functions, including migration and survival, by reprogramming the immune responses in pathologic tissues and promoting the innate immune functions of neutrophils, macrophages, and dendritic cells to the disadvantage of adaptive immunity. Strikingly, hypoxia and inflammatory signals share selected transcriptional events, including the activation of members of both the hypoxia-inducible factor and nuclear factor κB families, which may converge to activate specific cell programs. Here, we review the mechanisms of innate immunity adaptation to hypoxia, their role in disease, as well as new perspectives for their therapeutic targeting.