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
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    • "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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    • "Tissue oxygen tension is also a critical modulator of phenotype switching and metabolic alterations in tissue macrophages. HIF1␣-mediated differentiation of macrophage to the M1 phenotype and corresponding upregulation of anerobic glycolytic genes in inflamed tissues suggest critical roles for cellular metabolism and tissue oxygen levels in modulating cell function (Nizet and Johnson, 2009; Shapiro et al., 2011). It is important to note that M1 macrophages can transform into M2 macrophages during the Fig. 1. "
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    • "Secondly, hypoxia induces production of the hypoxia inducible factor, which also promotes the uncoupling of NOS [81–83] as well as the activation of arginase-2 [84]. This uncoupling simultaneously produces O2− and NO [85], leading to additional ONOO− generation [69, 70, 76, 86]. "
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