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HIF-mediated innate immune responses: cell signaling and therapeutic implications

Authors Harris A, Thompson AR, Whyte M, Walmsley S

Received 24 January 2014

Accepted for publication 28 February 2014

Published 24 May 2014 Volume 2014:2 Pages 47—58

DOI https://doi.org/10.2147/HP.S50269

Checked for plagiarism Yes

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Peer reviewer comments 6


Alison J Harris, AA Roger Thompson, Moira KB Whyte, Sarah R Walmsley

Academic Unit of Respiratory Medicine, Department of Infection and Immunity, University of Sheffield, Sheffield, UK

Abstract: Leukocytes recruited to infected, damaged, or inflamed tissues during an immune response must adapt to oxygen levels much lower than those in the circulation. Hypoxia inducible factors (HIFs) are key mediators of cellular responses to hypoxia and, as in other cell types, HIFs are critical for the upregulation of glycolysis, which enables innate immune cells to produce adenosine triphosphate anaerobically. An increasing body of evidence demonstrates that hypoxia also regulates many other innate immunological functions, including cell migration, apoptosis, phagocytosis of pathogens, antigen presentation and production of cytokines, chemokines, and angiogenic and antimicrobial factors. Many of these functions are mediated by HIFs, which are not only stabilized posttranslationally by hypoxia, but also transcriptionally upregulated by inflammatory signals. Here, we review the role of HIFs in the responses of innate immune cells to hypoxia, both in vitro and in vivo, with a particular focus on myeloid cells, on which the majority of studies have so far been carried out.

Keywords: hypoxia, neutrophils, monocytes, macrophages


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