NOX2-Derived Reactive Oxygen Species Control Inflammation during Leishmania amazonensis Infection by Mediating Infection-Induced Neutrophil Apoptosis.

Autor: Carneiro MBH; Snyder Institute for Chronic Diseases, Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 4Z6, Canada.; Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil., Roma EH; Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil.; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852; and., Ranson AJ; Snyder Institute for Chronic Diseases, Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 4Z6, Canada., Doria NA; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852; and., Debrabant A; Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD 20993., Sacks DL; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852; and., Vieira LQ; Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil., Peters NC; Snyder Institute for Chronic Diseases, Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 4Z6, Canada; ncpeters@ucalgary.ca.
Jazyk: angličtina
Zdroj: Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2018 Jan 01; Vol. 200 (1), pp. 196-208. Date of Electronic Publication: 2017 Nov 20.
DOI: 10.4049/jimmunol.1700899
Abstrakt: Reactive oxygen species (ROS) produced by NADPH phagocyte oxidase isoform (NOX2) are critical for the elimination of intracellular pathogens in many infections. Despite their importance, the role of ROS following infection with the eukaryotic pathogen Leishmania has not been fully elucidated. We addressed the role of ROS in C57BL/6 mice following intradermal infection with Leishmania amazonensis. Despite equivalent parasite loads compared with wild-type (WT) mice, mice deficient in ROS production by NOX2 due to the absence of the gp91 subunit (gp91 phox-/- ) had significantly more severe pathology in the later stages of infection. Pathology in gp91 phox-/- mice was not associated with alterations in CD4 + T cell-mediated immunity but was preceded by enhanced neutrophil accumulation at the dermal infection site. Ex vivo analysis of infected versus uninfected neutrophils revealed a deficiency in infection-driven apoptosis in gp91 phox-/- mice versus WT mice. gp91 phox-/- mice presented with higher percentages of healthy or necrotic neutrophils but lower percentages of apoptotic neutrophils at early and chronic time points. In vitro infection of gp91 phox-/- versus WT neutrophils also revealed reduced apoptosis and CD95 expression but increased necrosis in infected cells at 10 h postinfection. Provision of exogenous ROS in the form of H 2 O 2 reversed the necrotic phenotype and restored CD95 expression on infected gp91 phox-/- neutrophils. Although ROS production is typically viewed as a proinflammatory event, our observations identify the importance of ROS in mediating appropriate neutrophil apoptosis and the importance of apoptosis in inflammation and pathology during chronic infection.
(Copyright © 2017 by The American Association of Immunologists, Inc.)
Databáze: MEDLINE
Externí odkaz: