Alveolar macrophages protect mice from MERS-CoV-induced pneumonia and severe disease

Rudragouda Channappanavar; Muneeswaran Selvaraj; Sunil More; Stanley Perlman

doi:10.1177/03009858221095270

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Alveolar macrophages protect mice from MERS-CoV-induced pneumonia and severe disease

Journal article

Open access

Peer reviewed

Alveolar macrophages protect mice from MERS-CoV-induced pneumonia and severe disease

Rudragouda Channappanavar, Muneeswaran Selvaraj, Sunil More and Stanley Perlman

Veterinary pathology, Vol.59(4), pp.627-638

05/02/2022

DOI: 10.1177/03009858221095270

PMID: 35499307

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Abstract

Emerging and re-emerging human coronaviruses (hCoVs) cause severe respiratory illness in humans, but the basis for lethal pneumonia in these diseases is not well understood. Alveolar macrophages (AMs) are key orchestrators of host antiviral defense and tissue tolerance during a variety of respiratory infections, and AM dysfunction is associated with severe COVID-19. In this study, using a mouse model of Middle East respiratory syndrome coronavirus (MERS-CoV) infection, we examined the role of AMs in MERS pathogenesis. Our results show that depletion of AMs using clodronate (CL) liposomes significantly increased morbidity and mortality in human dipeptidyl peptidase 4 knock-in (hDPP4-KI) mice. Detailed examination of control and AM-depleted lungs at different days postinfection revealed increased neutrophil activity but a significantly reduced MERS-CoV-specific CD4 T-cell response in AM-deficient lungs during later stages of infection. Furthermore, enhanced MERS severity in AM-depleted mice correlated with lung inflammation and lesions. Collectively, these data demonstrate that AMs are critical for the development of an optimal virus-specific T-cell response and controlling excessive inflammation during MERS-CoV infection.

Immunology

T-cells

innate immunity

inflammatory monocytes

alveolar macrophages

Middle East respiratory syndrome coronavirus

mice

neutrophils

COVID-19

Details

Title: Subtitle: Alveolar macrophages protect mice from MERS-CoV-induced pneumonia and severe disease
Creators: Rudragouda Channappanavar - Oklahoma State University
Muneeswaran Selvaraj - Oklahoma State University
Sunil More - Oklahoma State University
Stanley Perlman - University of Iowa
Resource Type: Journal article
Publication Details: Veterinary pathology, Vol.59(4), pp.627-638
DOI: 10.1177/03009858221095270
PMID: 35499307
NLM abbreviation: Vet Pathol
eISSN: 1544-2217
Grant note: DOI: 10.13039/100000060, name: National Institute of Allergy and Infectious Diseases, award: NIH P01 AI060699 and RO1 AI129269; name: Oklahoma State University, College of Veterinary Medicine, Oklahoma Center for Respiratory and Infectious Disease (OCRID) Centers of Biomedical Research Excellence, award: NIH P20GM103648 and NIH AG060222
Language: English
Date published: 05/02/2022
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9984256060302771

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