Interdependence of hypoxic and innate immune response

Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
Nature Reviews Immunology (Impact Factor: 34.99). 10/2009; 9(9):609-17. DOI: 10.1038/nri2607
Source: PubMed


Hypoxia-inducible factor (HIF) is an important transcriptional regulator of cell metabolism and the adaptation to cellular stress caused by oxygen deficiency (hypoxia). Phagocytic cells have an essential role in innate immune defence against pathogens and this is a battle that takes place mainly in the hypoxic microenvironments of infected tissues. It has now become clear that HIF promotes the bactericidal activities of phagocytic cells and supports the innate immune functions of dendritic cells, mast cells and epithelial cells. In response to microbial pathogens, HIF expression is upregulated through pathways involving the key immune response regulator nuclear factor-kappaB, highlighting an interdependence of the innate immune and hypoxic responses to infection and tissue damage. In turn, HIF-driven innate immune responses have important consequences for both the pathogen and the host, such that the tissue microenvironment fundamentally influences susceptibility to infectious disease.

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Available from: Randall S Johnson, Mar 26, 2014
    • "However , activation of Hypoxia Inducible Factor 1 (HIF-1α) is a general phenomenon associated with the hypoxic regions of neoplasms while also being induced by lipopolysaccharides and other compounds produced by bacteria (Werth et al., 2010). This is because HIF-1α is associated with the host's innate immune functions in order to help the specialized phagocytic cells function in the hypoxic microenvironments of infected tissues (Nizet and Johnson, 2009; Zinkernagel et al., 2007). Thus, bacteria in the microenvironment of the tumor would effectively prepare the neoplasm against hypoxia as well as inflammation, since HIF-1α also has a positive association with the expression of the previously discussed aldehyde dehydrogenase (Tiezzi et al., 2013). "
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    • "Importantly, when recruited to tissue sites of infection or inflammation, macrophages immediately encounter a decreasing oxygen gradient, which leads to stabilization of hypoxia inducible factor-1 alpha (HIF-1) protein. This protein is then responsible for enhanced expression of innate immune response genes and molecules involved in macrophage recruitment and activation (described above) (Burke et al., 2003; Talks et al., 2000; Angele et al., 1999; Nizet and Johnson, 2009; Murdoch et al., 2005; Wang et al., 2006). "
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