Hypoxia inducible factor 1α: A critical factor for the immune response to pathogens and Leishmania

Organisms typically react to foreign pathogens by initiating an inflammatory response. However, in order to limit inflammatory tissue injury, it is essential for the organism to maintain the balance between inflammatory and anti-inflammatory responses. Dysregulation of this process can result in the strong inhibition of protective pro-inflammatory responses, and ultimately in pathogen persistence. Chronic infections are often associated with inflammation and tissue disruption. Inflamed tissues are characterized by low levels of oxygen and glucose, a microenvironment that triggers the stabilization of the hypoxia-inducible transcription factor HIF-1α. HIF-1α is the master regulator of the response to hypoxia. Here, we review the role of HIF-1α in the immune response to various pathogens and we highlight how certain microorganisms, including Leishmania parasites, have evolved to hijack the HIF-1 pathway to their advantage.