Critical role of phospholipase A2 group IID in age-related susceptibility to severe acute respiratory syndrome-CoV infection

Rahul Vijay; Xiaoyang Hua; David K Meyerholz; Yoshimi Miki; Kei Yamamoto; Michael Gelb; Makoto Murakami; Stanley Perlman

doi:10.1084/jem.20150632

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Critical role of phospholipase A2 group IID in age-related susceptibility to severe acute respiratory syndrome-CoV infection

Journal article

Open access

Peer reviewed

Critical role of phospholipase A2 group IID in age-related susceptibility to severe acute respiratory syndrome-CoV infection

Rahul Vijay, Xiaoyang Hua, David K Meyerholz, Yoshimi Miki, Kei Yamamoto, Michael Gelb, Makoto Murakami and Stanley Perlman

The Journal of experimental medicine, Vol.212(11), pp.1851-1868

10/19/2015

DOI: 10.1084/jem.20150632

PMCID: PMC4612096

PMID: 26392224

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Abstract

Oxidative stress and chronic low-grade inflammation in the lungs are associated with aging and may contribute to age-related immune dysfunction. To maintain lung homeostasis, chronic inflammation is countered by enhanced expression of proresolving/antiinflammatory factors. Here, we show that age-dependent increases of one such factor in the lungs, a phospholipase A2 (PLA2) group IID (PLA2G2D) with antiinflammatory properties, contributed to worse outcomes in mice infected with severe acute respiratory syndrome-coronavirus (SARS-CoV). Strikingly, infection of mice lacking PLA2G2D expression (Pla2g2d(-/-) mice) converted a uniformly lethal infection to a nonlethal one (>80% survival), subsequent to development of enhanced respiratory DC migration to the draining lymph nodes, augmented antivirus T cell responses, and diminished lung damage. We also observed similar effects in influenza A virus-infected middle-aged Pla2g2d(-/-) mice. Furthermore, oxidative stress, probably via lipid peroxidation, was found to induce PLA2G2D expression in mice and in human monocyte-derived macrophages. Thus, our results suggest that directed inhibition of a single inducible phospholipase, PLA2G2D, in the lungs of older patients with severe respiratory infections is potentially an attractive therapeutic intervention to restore immune function.

Disease Susceptibility

Age Factors

Oxidative Stress

Group II Phospholipases A2 - physiology

Humans

Mice, Inbred C57BL

Dendritic Cells - physiology

CD11c Antigen - analysis

Immunity, Innate

Severe Acute Respiratory Syndrome - etiology

Animals

Mice

Lipids - analysis

Lung - immunology

Details

Title: Subtitle: Critical role of phospholipase A2 group IID in age-related susceptibility to severe acute respiratory syndrome-CoV infection
Creators: Rahul Vijay - Interdisciplinary Program in Immunology and Department of Otolaryngology, Department of Pathology, and Department of Microbiology, University of Iowa, Iowa City, IA 52242
Xiaoyang Hua - Interdisciplinary Program in Immunology and Department of Otolaryngology, Department of Pathology, and Department of Microbiology, University of Iowa, Iowa City, IA 52242
David K Meyerholz - Interdisciplinary Program in Immunology and Department of Otolaryngology, Department of Pathology, and Department of Microbiology, University of Iowa, Iowa City, IA 52242
Yoshimi Miki - Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan
Kei Yamamoto - Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan
Michael Gelb - Department of Chemistry and Department of Biochemistry, University of Washington, Seattle, WA 98195 Department of Chemistry and Department of Biochemistry, University of Washington, Seattle, WA 98195
Makoto Murakami - Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Saitama 332-0012, Japan
Stanley Perlman - Interdisciplinary Program in Immunology and Department of Otolaryngology, Department of Pathology, and Department of Microbiology, University of Iowa, Iowa City, IA 52242 Interdisciplinary Program in Immunology and Department of Otolaryngology, Department of Pathology, and Department of Microbiology, University of Iowa, Iowa City, IA 52242 Stanley-Perlman@uiowa.edu
Resource Type: Journal article
Publication Details: The Journal of experimental medicine, Vol.212(11), pp.1851-1868
DOI: 10.1084/jem.20150632
PMID: 26392224
PMCID: PMC4612096
NLM abbreviation: J Exp Med
ISSN: 0022-1007
eISSN: 1540-9538
Publisher: United States
Grant note: AI091322 / NIAID NIH HHS R01 HL036235 / NHLBI NIH HHS AI060699 / NIAID NIH HHS R37 HL036235 / NHLBI NIH HHS HL36235 / NHLBI NIH HHS R01 AI091322 / NIAID NIH HHS P01 AI060699 / NIAID NIH HHS P30 DK054759 / NIDDK NIH HHS
Language: English
Date published: 10/19/2015
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Otolaryngology; Infectious Disease (Pediatrics)
Record Identifier: 9983777353602771

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