{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T18:30:46Z","timestamp":1777919446002,"version":"3.51.4"},"reference-count":88,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T00:00:00Z","timestamp":1651449600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["NIH P01 AI060699 and RO1 AI129269"],"award-info":[{"award-number":["NIH P01 AI060699 and RO1 AI129269"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"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"],"award-info":[{"award-number":["NIH P20GM103648 and NIH AG060222"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Vet Pathol"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:p>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. 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