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 (CL₂MDP) 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.