title: Susceptibility to infection and inflammatory response following influenza virus (H1N1, A/PR/8/34) challenge: role of macrophages.
abstract: The precise role that macrophages play in both influenza-induced pathology and the host's cytokine-mediated response to infection remains largely unknown. We examined the effects of lung macrophage depletion on susceptibility to influenza virus (H1N1, A/PR/8/34) infection and how this relates to the inflammatory cytokine response in the lungs. ICR mice were administered 100 μL of clodronate (CL(2)MDP) or PBS-encapsulated liposomes via an intranasal route 2 days before infection. Then, mice were intranasally inoculated with influenza virus and monitored for morbidity, mortality, and symptom severity for 21 days. Additional mice were sacrificed at 2 and 5 days postinfection, and lung tissue was analyzed for viral replication and for gene expression and protein concentration of interleukin-1β (IL-1β), IL-6, and TNF-α. Macrophage depletion increased morbidity, mortality, and symptom severity (P < 0.05) and viral replication at 2 and 5 days postinfection (P < 0.05). IL-1β, IL-6, and TNF-α mRNA was greater at day 2 (P < 0.05) and IL-6 and TNF-α was greater at day 5 postinfection (P < 0.05) in macrophage depleted mice. Macrophage depletion increased protein concentration of IL-1β and IL-6 at day 2 postinfection (P < 0.05). These data suggest that macrophages play a necessary role in controlling susceptibility to influenza virus and the host's cytokine-mediated response to influenza infection.
authors.affiliation: Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209. USA. angela.murphy@uscmed.sc.edu
authors.forename: E Angela
authors.initials: EA
authors.lastname: Murphy
authors.forename: J Mark
authors.initials: JM
authors.lastname: Davis
authors.forename: Jamie L
authors.initials: JL
authors.lastname: McClellan
authors.forename: Martin D
authors.initials: MD
authors.lastname: Carmichael
authors.forename: Nico Van
authors.initials: NV
authors.lastname: Rooijen
authors.forename: J David
authors.initials: JD
authors.lastname: Gangemi
mesh_terms: D000818:Animals; D001781:Blood Component Removal; D004002:Clodronic Acid / Q000008:administration & dosage / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004198:Disease Susceptibility; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D053118:Influenza A Virus, H1N1 Subtype / Q000472:pathogenicity / Q000502:physiology*; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology; D008168:Lung / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D051379:Mice; D008813:Mice, Inbred ICR; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000821:virology; D012367:RNA, Viral / Q000032:analysis*; D014779:Virus Replication
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D012367:RNA, Viral; D004002:Clodronic Acid