Differences in intracellular killing of Salmonella typhimurium by macrophages of inbred mouse strains

Abstract

Inbred strains of mice differ in susceptibility to infection by intracellular bacterial pathogens such as Salmonella typhimurium and Listeria monocytogenes. Mice of the C57BL/10 strain, for example, die after intraperitoneal exposure to fewer than 100 Salmonella typhimurium, whereas CBA mice survive a challenge with 5 × 103 of this species. The strain dependence of susceptibility to infection by Salmonella typhimurium is genetically controlled (1). At least one non-H-2 linked gene, located on chromosome 1 and designated Ity (Immunity to typhimurium), regulates the initial in vivo proliferation rate of the bacteria in the spleen and liver (2–8). The Ity gene is expressed by 24 hours after infection, and mice that carry the dominant allelle (Ityr) are able to restrict bacterial multiplication and survive the first phase of the infection. The cells involved in the expression of the gene activity are reported to be bone marrow derived (9) and sensitive to silica treatment (10). Furthermore, it has been shown that the presence of functional T lymphocytes is not required for expression of the trait (11). These findings suggest that macrophages are the effector cells. The inability of susceptible mouse strains to restrict the initial bacterial proliferation in the early phase of infection before establishment of an immune response could therefore be caused by, for example, 1) less efficient recruitment of monocytes to the inflammatory exudate, 2) macrophage dysfunction with respect to the handling of microorganisms (i.e., phagocytosis, intracellular killing). In addition, differences in function between macrophages from Salmonella resistant and susceptible mice could be acquired very early in the infection. The results of in vitro studies on the intracellular killing of Salmonella typhimurium by resident macrophages of resistant and susceptible mouse strains have been divergent: some authors were unable to demonstrate differences between macrophages from resistant and susceptible mice (5, 6, 8), whereas one author reported that peritoneal macrophages of resistant BRVR mice killed ingested Salmonella more efficiently than macrophages of susceptible BSVS mice did (12).