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Depletion of alveolar macrophages ameliorates virus-induced disease following a pulmonary coronavirus infection
Journal article   Open access   Peer reviewed

Depletion of alveolar macrophages ameliorates virus-induced disease following a pulmonary coronavirus infection

Stacey M Hartwig, Kaitlyn M Holman and Steven M Varga
PloS one, Vol.9(3), pp.e90720-e90720
2014
DOI: 10.1371/journal.pone.0090720
PMCID: PMC3946553
PMID: 24608125
url
https://doi.org/10.1371/journal.pone.0090720View
Published (Version of record) Open Access

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.
CD4-Positive T-Lymphocytes - metabolism Cells, Cultured Murine hepatitis virus - pathogenicity Coronavirus Infections - immunology Mice, Inbred C3H Lung - virology Animals Coronavirus CD8-Positive T-Lymphocytes - metabolism Female Mice Lung - immunology Macrophages, Alveolar - immunology

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