N. brasiliensis priming in three different inbred strains of mice provides protection to influenza A virus challenge in a strain dependent manner 2307446

Abstract Introduction N. brasiliensis (Nb) is a helminth that induces extensive type 2 remodeling in the lung due to its migration route through the host. Recent studies have investigated how exposure to helminths alters the immune response to challenge viral infection, but genetic variation is rarely studied. The aim of this study was to investigate how genetic variation impacts helminth-induced remodeling and its effects on subsequent viral challenge utilizing influenza A virus. Methods Females of three different inbred strains of mice were used in this study: BALB/c, C57BL/6, and B10.BR, and were primed with 500 Nb larvae subcutaneously on day -28 and allowed to recover naturally before being infected with influenza A/PR/8 virus on day 0. Mice were monitored for 10 days for weight loss and survival. Mice were also taken down on day 0 following priming to analyze the lung environment. Lung lobes were taken for histopathology, a multiplex cytokine and chemokine panel, and spectral flow cytometry. Results Priming with Nb was found to improve weight loss and survival following challenge with influenza A/PR/8 virus. However, there was strain-specific protection, namely BALB/c mice recovered much slower than C57BL/6 and B10.BR mice. Primed only mice showed varied lung environments that were distinct from each other. Particularly, BALB/c mice had decreased alternatively activated macrophages and dendritic cells, and increased Ly6G+ macrophages from spectral flow cytometry data. The histopathology also showed they had decreased inflammation and increased emphysema-like characteristics compared to the C57BL/6 and B10.BR mice. Conclusion Based on our study, the extent of protection to influenza A challenge infection in Nb-primed mice is dependent on genotype. These results expand our understanding on how the contribution of an individual’s infection history and genetics can influence the response to subsequent viral infection. Funding Source 1ZIAAI001386-01 Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)