Genetic Control of the Innate Resistance of Mice to Salmonella typhimurium: Expression of the Ity Gene in Peritoneal Macrophages Isolated In Vitro
Abstract
The mouse Chromosome 1 locus Ity regulates the extent to which Salmonella typhimurium replicates within the reticuloendothelial cell system (RES) during the first days of infection. If mice are homozygous for the Ity(expn s) susceptibility allele, the gram negative bacterium undergoes rapid net multiplication in the liver and spleen, a severe secondary bacteremia ensues, and mice die of a typhoid fever-like disease by day 10 of infection. Animals that are homozygous or heterozygousfor the resistance allele, Ity(expn r), control net bacterial replication and survive the first phase of murine typhoid. Indirect studies have implicated the resident macrophage as the effector cell for regulation of early in vivo salmonellae growth. To verify this supposition and to evaluate the phenotypic expression of Ity, an in vitro assay was developed to compare the fate of S. typhimurium within Ity(expn r) and Ity(expn s) macrophages. Resident peritoneal macrophages were used from inbred Ity(expn r) and Ity(expn s) mice and from Ity congenic mice. With these mice and through the use of radiolabeled S. typhimurium, indirect immunofluorescence antibody (IFA), light microscopy, transmission electron microscopy (T.E.M.), and avirulent non-replicating mutants of the bacterium the following conclusions were reached. The phagocytosis of S. typhimurium by Ity(expn r) and Ity(expn s) was the same. At the ultrastructural level both Ity(expn r) and Ity(expn s) macrophages phagocytized the bacterium into phagosomes, which subsequently fused with lysosomes to form phagolysosomes. After 24 hours of infection there were more cell-associated S. typhimurium in Ity(expn s) peritoneal macrophages than in Ity(expn r) cells. Ity(expn r) macrophages killed intracellular salmonellae more efficiently than did Ity(expn s) macrophages.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 20, 1984
- Accession Number
- AD1010721
Entities
People
- Christopher R. Lissner
Organizations
- Uniformed Services University of the Health Sciences