title: Depletion of alveolar macrophages ameliorates virus-induced disease following a pulmonary coronavirus infection.
abstract: Coronaviruses cause respiratory disease in humans that can range from mild to severe. However, the pathogenesis of pulmonary coronavirus infections is poorly understood. Mouse hepatitis virus type 1 (MHV-1) is a group 2 coronavirus capable of causing severe morbidity and mortality in highly susceptible C3H/HeJ mice. We have previously shown that both CD4 and CD8 T cells play a critical role in mediating MHV-1-induced disease. Here we evaluated the role of alveolar macrophages (AM) in modulating the adaptive immune response and subsequent disease. Depletion of AM using clodronate liposomes administered prior to MHV-1 infection was associated with a significant amelioration of MHV-1-induced morbidity and mortality. AM depletion resulted in a decreased number of virus-specific CD4 T cells in the lung airways. In addition, a significant increase in the frequency and total number of Tregs in the lung tissue and lung airways was observed following MHV-1 infection in mice depleted of AM. Our results indicate that AM play a critical role in modulating MHV-1-induced morbidity and mortality.
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Stacey M
authors.initials: SM
authors.lastname: Hartwig
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Kaitlyn M
authors.initials: KM
authors.lastname: Holman
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, Iowa, United States of America; Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, United States of America; Department of Pathology, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Varga
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002478:Cells, Cultured; D017934:Coronavirus; D018352:Coronavirus Infections / Q000276:immunology*; D005260:Female; D008168:Lung / Q000276:immunology / Q000821:virology; D016676:Macrophages, Alveolar / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D006517:Murine hepatitis virus / Q000472:pathogenicity