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. 1. Introduction Salmonella are intracellular gram-negative bacteria found ubiquitously in nature and still representing a major public health problem [1]. Over 16 million cases of salmonella are associated with enteric fever, and 600000 deaths from untreated infection are reported annually in developing countries worldwide [1]. An increased incidence of nontyphoid salmonella infections with most cases tracing back to food contamination is experienced in industrialized countries [1]. The risks and outcome of salmonella infection are influenced by many factors such as antimicrobials, integrity of the host endogenous flora, loss of the gastric acid barrier, HIV infection, and host genetics [1]. Some of mouse salmonella resistance genes such as Ity, Lps, and xid were widely studied in the past decades [2–4]. Some new loci, such as Tbc2 (D9Mit89), were identified recently [5]. However, the links between susceptible host phenotype and newly identified locus were not studied in detail. Salmonella
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