Abstract
Alveolar macrophage (AM) Toll-like Receptors (TLRs) signaling drives inflammation and pathogenic neutrophilic infiltrate during neonatal murine Influenza virus infection
The Journal of immunology (1950), v 212(1_Supplement), pp 1136-1136_5040
01 May 2024
Abstract
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.
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Details
- Title
- Alveolar macrophage (AM) Toll-like Receptors (TLRs) signaling drives inflammation and pathogenic neutrophilic infiltrate during neonatal murine Influenza virus infection
- Creators
- Abhishek Rao - Drexel UniversityOgan Kumova - Center for Biologics Evaluation and ResearchAbigail Onufer - Drexel UniversityJudy Pascasio - Drexel UniversityAlison Carey - Drexel University
- Publication Details
- The Journal of immunology (1950), v 212(1_Supplement), pp 1136-1136_5040
- Publisher
- American Association of Immunologists (AAI)
- Resource Type
- Abstract
- Language
- English
- Academic Unit
- Microbiology and Immunology; Pediatrics
- Other Identifier
- 991021959240404721