Lipopolysaccharide (LPS) protects from a normally lethal dose of respiratory viral infection and affects post-airway disease in a dose dependent manner

Abstract

Abstract Rationale Respiratory diseases are major public health concerns and leading causes of death and disability in the world. Understanding anti-viral immune responses is crucial to alleviate morbidity and mortality of respiratory infections. Previous data using our Sendai virus (SeV, murine parainfluenza virus type 1) mouse model suggested pretreatment of C57BL6 wild-type (WT) mice with 3μg lipopolysaccharide (LPS) reduced mortality from a normally lethal dose of SeV (2×106pfu) by half. This study was undertaken to identify the minimal effective dose for survival from the normally lethal SeV and determine its effects on subsequent airway disease. Methods WT mice were intranasally (i.n.) inoculated with 30 μL of 0.01–3 μg LPS or PBS 24 hours before lethal dose of SeV i.n. and survival determined. In surviving mice, invasive measurement of airway hyper-reactivity (AHR) was determined on d21 post-viral inoculation. Results LPS mediated survival and AHR were dose dependent (p<0.0001 comparing all groups, Mantel-Cox for survival and ANOVA for AHR). Mice receiving lower doses of LPS (0.03 and 0.1 μg) had increased survival (92±8% and 67±10% survival, respectively) and decreased AHR compared to those with the highest doses (n≥5 mice per dose with up to 4 experimental repeats). Conclusion LPS mediated survival from a lethal paramyxoviral infection is greatest with lower doses of LPS (0.1–0.03 μg). These doses have been associated with development of atopic disease (Eisenbarth SC, J Exp Med. 2002). We are currently undertaking studies to determine the mechanism(s) through which low dose LPS inhibits mortality from normally lethal SeV dose and how this reduces post-SeV atopy.