title: Depletion of alveolar macrophages prolongs survival in response to acute pneumovirus infection.
abstract: Alveolar macrophages are immunoregulatory effector cells that interact directly with respiratory virus pathogens in vivo. We examined the role of alveolar macrophages in acute infection with pneumonia virus of mice (PVM), a rodent pneumovirus that replicates the clinical sequelae of severe human respiratory syncytial virus disease. We show that PVM replicates in primary mouse macrophage culture, releasing infectious virions and proinflammatory cytokines. Alveolar macrophages isolated from PVM-infected mice express activation markers Clec43 and CD86, cytokines TNFα, IL-1, IL-6, and numerous CC and CXC chemokines. Alveolar macrophage depletion prior to PVM infection results in small but statistically significant increases in virus recovery but paradoxically prolonged survival. In parallel, macrophage depleted PVM-infected mice exhibit enhanced NK cell recruitment and increased production of IFNγ by NK, CD4(+) and CD8(+) T cells. These results suggest a protective, immunomodulatory role for IFNγ, as overproduction secondary to macrophage depletion may promote survival despite increased virus recovery.
authors: Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Peter
authors: P
authors: Rigaux
authors: Kristin E
authors: KE
authors: Killoran
authors: Zhijun
authors: Z
authors: Qiu
authors: Helene F
authors: HF
authors: Rosenberg
mesh_terms: D000818:Animals; D051940:B7-2 Antigen / Q000378:metabolism; D015415:Biomarkers; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D002478:Cells, Cultured; D004002:Clodronic Acid / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D016676:Macrophages, Alveolar / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D029122:Murine pneumonia virus / Q000276:immunology*; D018186:Pneumovirus Infections / Q000276:immunology* / Q000378:metabolism
chemical_list: D051940:B7-2 Antigen; D015415:Biomarkers; D050071:Bone Density Conservation Agents; D016207:Cytokines; D037181:Lectins, C-Type; D004002:Clodronic Acid; D007371:Interferon-gamma