Lipopolysaccharide pre-treatment prevents viral induced death by priming macrophages for a robust anti-viral immune response

Abstract

Abstract Rationale Respiratory viruses are an increasing public health burden. Using Sendai virus (SeV, murine parainfluenza virus type 1), previous data indicate that pretreatment of C57BL6 wild-type (WT) mice with 0.1μg of lipopolysaccharide (LPS) prevented mortality from a normally lethal SeV infection. However, the mechanism by which LPS pre-treatment confers this survival advantage is unknown. LPS is a potent activator of macrophages. We hypothesized that LPS prevents viral induced death by stimulating the recruitment of macrophages, which could drive a more robust anti-viral immune response and subsequent survival. Therefore, we examined the change in lung macrophage subsets with LPS pretreatment of SeV infected mice. Methods WT mice were inoculated with 30 μL of 0.1 μg LPS or PBS i.n. 24 hours before SeV (2e6 pfu). After LPS sensitization, lungs were harvested at 6 hours, 24 hours, and days 1,3,5, and 7 post SeV infection (PI SeV); single lung cell suspensions isolated and stained for various innate immune cells by flow cytometry to assess the immune cells recruited by LPS. Results Mice pre-treated with LPS had a significant increase of alveolar macrophages (GR1- Siglec F+ CD11c+) at days 1 and 3 PI SeV (p=0.080 and p=0.0026, respectively; n≥6). Additionally, interstitial macrophages (GR1- Siglec F− CD11b+ CD11c+ F4/80+ MHCII+) were significantly increased at days 0 and 3 PI SeV (p=0.025 and p=0.019 respectively; n≥6). The LPS effect was no longer significant by day 5 PI SeV. Conclusion . LPS pretreatment of mice increases macrophages early during the SeV infection. Further studies will be needed to determine if the increase in these macrophages provides the protection from viral induced mortality seen in our model and the cytokines produced. This work was supported by the Abigail Wexner Research Institute at Nationwide Children’s Hospital (MHG).