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J Mol Biol. 2016 Aug 28;428(17):3495-513. doi: 10.1016/j.jmb.2016.04.032. Epub 2016 May 12.

Interferon-Inducible GTPases in Host Resistance, Inflammation and Disease.

Author information

1
Department of Molecular Genetics and Microbiology, and Immunology, Duke University Medical Center, Durham, NC 27710, USA.
2
Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
3
Department of Medicine, Duke University, Durham, NC 27708, USA; Department of Molecular Genetics and Microbiology, and Immunology, Duke University, Durham, NC 27708, USA; Center for the Study of Aging, Duke University, Durham, NC 27708, USA; Geriatric Research and Education and Clinical Center, Veteran Affairs Medical Center, Durham, NC 27710, USA. Electronic address: gregory.taylor@dm.duke.edu.
4
Department of Molecular Genetics and Microbiology, and Immunology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: jorn.coers@duke.edu.

Abstract

Cell-autonomous immunity is essential for host organisms to defend themselves against invasive microbes. In vertebrates, both the adaptive and the innate branches of the immune system operate cell-autonomous defenses as key effector mechanisms that are induced by pro-inflammatory interferons (IFNs). IFNs can activate cell-intrinsic host defenses in virtually any cell type ranging from professional phagocytes to mucosal epithelial cells. Much of this IFN-induced host resistance program is dependent on four families of IFN-inducible GTPases: the myxovirus resistance proteins, the immunity-related GTPases, the guanylate-binding proteins (GBPs), and the very large IFN-inducible GTPases. These GTPase families provide host resistance to a variety of viral, bacterial, and protozoan pathogens through the sequestration of microbial proteins, manipulation of vesicle trafficking, regulation of antimicrobial autophagy (xenophagy), execution of intracellular membranolytic pathways, and the activation of inflammasomes. This review discusses our current knowledge of the molecular function of IFN-inducible GTPases in providing host resistance, as well as their role in the pathogenesis of autoinflammatory Crohn's disease. While substantial advances were made in the recent past, few of the known functions of IFN-inducible GTPases have been explored in any depth, and new functions await discovery. This review will therefore highlight key areas of future exploration that promise to advance our understanding of the role of IFN-inducible GTPases in human diseases.

KEYWORDS:

Crohn's disease; GBP; IRG; IRGM; Inflammasome

PMID:
27181197
PMCID:
PMC5010443
DOI:
10.1016/j.jmb.2016.04.032
[Indexed for MEDLINE]
Free PMC Article

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