Giuseppe
Emeritus
[Source: PLoS ONE, full text: (LINK). Abstract, edited.]
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IL-22 Signaling Contributes to West Nile Encephalitis Pathogenesis
Penghua Wang<SUP>1</SUP><SUP>#</SUP><SUP>*</SUP>, Fengwei Bai<SUP>1</SUP><SUP>,</SUP><SUP>7</SUP><SUP>#</SUP>, Lauren A. Zenewicz<SUP>3</SUP><SUP>?</SUP>, Jianfeng Dai<SUP>1</SUP>, David Gate<SUP>4</SUP>, Gong Cheng<SUP>1</SUP>, Long Yang<SUP>1</SUP>, Feng Qian<SUP>2</SUP>, Xiaoling Yuan<SUP>2</SUP>, Ruth R. Montgomery<SUP>2</SUP>, Richard A. Flavell<SUP>3</SUP><SUP>,</SUP><SUP>6</SUP>, Terrence Town<SUP>4</SUP><SUP>,</SUP><SUP>5</SUP>, Erol Fikrig<SUP>1</SUP><SUP>,</SUP><SUP>6</SUP>
<SUP></SUP>
1 Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America, 2 Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America, 3 Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America, 4 Regenerative Medicine Institute, Departments of Biomedical Sciences and Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, United States of America, 5 Department of Medicine, University of California Los Angeles, Los Angeles, California, United States of America, 6 Howard Hughes Medical Institute, Chevy Chase, Maryland, United States of America, 7 Department of Biological Sciences, University of Southern Mississippi, Hattiesburg, Mississippi, United States of America
Abstract
The Th17 cytokine, IL-22, regulates host immune responses to extracellular pathogens. Whether IL-22 plays a role in viral infection, however, is poorly understood. We report here that Il22<SUP>−/−</SUP> mice were more resistant to lethal West Nile virus (WNV) encephalitis, but had similar viral loads in the periphery compared to wild type (WT) mice. Viral loads, leukocyte infiltrates, proinflammatory cytokines and apoptotic cells in the central nervous system (CNS) of Il22<SUP>−/−</SUP> mice were also strikingly reduced. Further examination showed that Cxcr2, a chemokine receptor that plays a non-redundant role in mediating neutrophil migration, was significantly reduced in Il22<SUP>−/−</SUP> compared to WT leukocytes. Expression of Cxcr2 ligands, cxcl1 and cxcl5, was lower in Il22<SUP>−/−</SUP> brains than wild type mice. Correspondingly, neutrophil migration from the blood into the brain was attenuated following lethal WNV infection of Il22<SUP>−/−</SUP> mice. Our results suggest that IL-22 signaling exacerbates lethal WNV encephalitis likely by promoting WNV neuroinvasion.
Citation: Wang P, Bai F, Zenewicz LA, Dai J, Gate D, et al. (2012) IL-22 Signaling Contributes to West Nile Encephalitis Pathogenesis. PLoS ONE 7(8): e44153. doi:10.1371/journal.pone.0044153
Editor: Philip J. Norris, Blood Systems Research Institute, United States of America
Received: March 28, 2012; Accepted: July 30, 2012; Published: August 28, 2012
Copyright: ? 2012 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work is supported by National Institutes of Health grants AI-055749, AI-50031, HHSN272201100019C and AI-079348. EF and RAF are investigators of the Howard Hughes Medical Institute. TT is supported by National Institutes of Health/National Institute on Aging ?Pathway to Independence? awards (5R00AG029726-04 and 3R00AG029726-04S1) and is the inaugural holder of the Ben Winters Endowed Chair in Regenerative Medicine. PW is supported by a Career Development Award from Northeast Biodefense Center U54-AI057158-Lipkin. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: penghua.wang@yale.edu
# These authors contributed equally to this work.
?Current address: Department of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America
-Penghua Wang<SUP>1</SUP><SUP>#</SUP><SUP>*</SUP>, Fengwei Bai<SUP>1</SUP><SUP>,</SUP><SUP>7</SUP><SUP>#</SUP>, Lauren A. Zenewicz<SUP>3</SUP><SUP>?</SUP>, Jianfeng Dai<SUP>1</SUP>, David Gate<SUP>4</SUP>, Gong Cheng<SUP>1</SUP>, Long Yang<SUP>1</SUP>, Feng Qian<SUP>2</SUP>, Xiaoling Yuan<SUP>2</SUP>, Ruth R. Montgomery<SUP>2</SUP>, Richard A. Flavell<SUP>3</SUP><SUP>,</SUP><SUP>6</SUP>, Terrence Town<SUP>4</SUP><SUP>,</SUP><SUP>5</SUP>, Erol Fikrig<SUP>1</SUP><SUP>,</SUP><SUP>6</SUP>
<SUP></SUP>
1 Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America, 2 Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America, 3 Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America, 4 Regenerative Medicine Institute, Departments of Biomedical Sciences and Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, United States of America, 5 Department of Medicine, University of California Los Angeles, Los Angeles, California, United States of America, 6 Howard Hughes Medical Institute, Chevy Chase, Maryland, United States of America, 7 Department of Biological Sciences, University of Southern Mississippi, Hattiesburg, Mississippi, United States of America
Abstract
The Th17 cytokine, IL-22, regulates host immune responses to extracellular pathogens. Whether IL-22 plays a role in viral infection, however, is poorly understood. We report here that Il22<SUP>−/−</SUP> mice were more resistant to lethal West Nile virus (WNV) encephalitis, but had similar viral loads in the periphery compared to wild type (WT) mice. Viral loads, leukocyte infiltrates, proinflammatory cytokines and apoptotic cells in the central nervous system (CNS) of Il22<SUP>−/−</SUP> mice were also strikingly reduced. Further examination showed that Cxcr2, a chemokine receptor that plays a non-redundant role in mediating neutrophil migration, was significantly reduced in Il22<SUP>−/−</SUP> compared to WT leukocytes. Expression of Cxcr2 ligands, cxcl1 and cxcl5, was lower in Il22<SUP>−/−</SUP> brains than wild type mice. Correspondingly, neutrophil migration from the blood into the brain was attenuated following lethal WNV infection of Il22<SUP>−/−</SUP> mice. Our results suggest that IL-22 signaling exacerbates lethal WNV encephalitis likely by promoting WNV neuroinvasion.
Citation: Wang P, Bai F, Zenewicz LA, Dai J, Gate D, et al. (2012) IL-22 Signaling Contributes to West Nile Encephalitis Pathogenesis. PLoS ONE 7(8): e44153. doi:10.1371/journal.pone.0044153
Editor: Philip J. Norris, Blood Systems Research Institute, United States of America
Received: March 28, 2012; Accepted: July 30, 2012; Published: August 28, 2012
Copyright: ? 2012 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work is supported by National Institutes of Health grants AI-055749, AI-50031, HHSN272201100019C and AI-079348. EF and RAF are investigators of the Howard Hughes Medical Institute. TT is supported by National Institutes of Health/National Institute on Aging ?Pathway to Independence? awards (5R00AG029726-04 and 3R00AG029726-04S1) and is the inaugural holder of the Ben Winters Endowed Chair in Regenerative Medicine. PW is supported by a Career Development Award from Northeast Biodefense Center U54-AI057158-Lipkin. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: penghua.wang@yale.edu
# These authors contributed equally to this work.
?Current address: Department of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America
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