Local and Systemic Immune Responses to Salmonella in Genetically Susceptible I/St Mice after Mucosal Challenge

Abstract

It was previously demonstrated that mice of I/StSnEgYCit (I/St) strain are more susceptible to tuberculosis infection than A/SnYCit (A/Sn) mice, and this susceptibility was controlled by a few interacting QTLs mapped to chromosomes 3, 9, 17. It was also shown, that I/St mice displayed higher susceptibility to acute salmonella disease after intraperitoneal challenge with S. enterica serovar Typhimurium. Genetic mapping showed the involvement of Tbs2 (D9Mit89) loci in control of both salmonella and tuberculosis infections. In this study we define the immunological correlates of susceptibility in I/St mice after oral administration of S. enterica serovar Typhimurium. We found that resistance/susceptibility in I/St and A/Sn mice in our experiments correlated with differential pattern of early local and systemic responses of innate cells and specifically with higher involvement of Gr-1+ cells in local responses of resistant mice. This correlated with higher mucosal antibody production in A/Sn mice compared to I/St. I/St mice had predominant local involvement of CD11c+ cells and lack of mucosal antibodies. CD11c+ cells were the major type of cells that facilitated dissemination of salmonella to the target organs, while Gr-1+ cells contributed to exaggerated systemic inflammatory responses later in the course of infection. Our observations regarding the role of different cell populations in local and systemic immunity in susceptible and resistant mice are of importance for understanding of salmonella-induced cellular pathology and development of the strategy of its control.