Genetically resistant (Ityr) and susceptible (Itys) congenic mouse strains show similar cytokine responses following infection with Salmonella dublin.

Abstract

IFN-gamma, TNF-alpha, IL-1, and granulocyte-macrophage CSF (GM-CSF) play an important role in host resistance to infection with nontyphoid Salmonella. In mice, resistance to Salmonella is determined by alleles of the susceptibility gene, Nramp, which maps to the Ity/Lsh/Bcg locus and is expressed in macrophages. In vitro studies suggested that macrophages from Salmonella-susceptible mice (Itys phenotype) are impaired functionally in their ability to produce, or stimulate the production of, cytokines such as TNF-alpha and IFN-gamma. BALB/c and BALB/c.DBA2 Idh-lb-Ityr-Pep-3b mice are congenic strains that differ at the Ity/Lsh/Bcg locus and in their susceptibility to Salmonella infection. These strains were used to question whether differences in the host cytokine response determine the outcome of Salmonella infection in genetically susceptible and resistant mice. As reported in this work, the in vivo response to Salmonella dublin infection in both Itys and Ityr mice was characterized by increased expression of IFN-gamma, TNF-alpha, GM-CSF, IL-1 alpha, IL-2, IL-6, IL-10, and IL-12 p40. In contrast, expression of IL-4, IL-5, and TGF-beta 1 was not altered, or decreased, during the course of infection. Moreover, the kinetics and magnitude of the cytokine response following S. dublin infection were similar in susceptible Itys and resistant Ityr mice, even though the former group died while the latter survived the infection. Thus, in vivo cytokine responses that are associated with survival of Ityr mice following S. dublin infection do not confer protection in mice of the Itys phenotype.