Alveolar macrophage (AM) Toll-like Receptors (TLRs) signaling drives inflammation and pathogenic neutrophilic infiltrate during neonatal murine Influenza virus infection
Presentation Time: 04:45 PM - 05:00 PM
Abstract ID: 5040 - B
Presenting Author:
Abhishek S Rao , PhD candidate at Drexel Univ. Col. of Med.
Abstract:
Like human neonates, murine neonates are highly susceptible to influenza viral (IV) infection. AMs are tissue-resident immune cells which are activated through TLRs to initiate immune cell recruitment to the site of infection, critical for viral control. However, bystander damage can also occur in the delicate alveoli. Therefore, we hypothesized that AM TLRs contribute to neonatal murine IV pathogenesis via neutrophil recruitment. To determine the relative contribution of AM TLR signaling, we utilized the Cre-flox system to generate AM-specific TLR deletions (LysMCre-MyD88flox). Three-day-old transgenic mice were infected with influenza type A virus strain PR/8/34 (H1N1) and tracked for survival. LysMCre-MyD88flox neonates demonstrated improved survival (70%) compared to wild type (WT) (33%). Moreover, LysMCre-MyD88flox neonates had decreased inflammatory cytokine concentrations in the broncho-alveolar lavage (BAL) compared to WT, specifically IL-18, IL-6, TNF-α and myeloid recruiting chemokines MCP-1 and CXCL1. Flow analysis of the BAL revealed lower neutrophils in the LysMCre-MyD88flox group, consistent with the cytokine concentrations. To test the pathogenic role of neutrophils during IV infection, infected WT neonates were neutrophil-depleted and had improved survival (60% vs. 24%, isotype group). These findings suggest AM TLRs increase IV pathogenesis in neonatal mice and that TLR-blockade is a potential therapeutic target in this vulnerable population.
Alveolar macrophage (AM) Toll-like Receptors (TLRs) signaling drives inflammation and pathogenic neutrophilic infiltrate during neonatal murine Influenza virus infection
Category
Poster and Podium (Block Symposium)