Genetic linkage of resistance to Listeria monocytogenes with macrophage inflammatory responses.
The mobilization of adequate numbers of mononuclear phagocytes to inflammatory foci was measured in Listeria-resistant and Listeria-sensitive mice. Resistant strains, such as B10.A, were found to have a 2- to 3-fold greater accumulation of peritoneal macrophages after i.p. treatment with a variety of nonspecific inflammatory stimuli in comparison to sensitive strains, such s A/J. In addition to low macrophage inflammatory responses, A/J mice had fewer resident peritoneal macrophages. Moreover, measurement of chemotaxis in vitro of equal numbers of thioglycollate-induced macrophages showed cells from A/J mice to be less responsive to complement-derived chemotactic factors. Thus, the mononuclear phagocyte systems of resistant B10.A and sensitive A/J mice were quantitatively and qualitatively different. A survey of inbred mouse strains revealed that these differences were not peculiar to A strain mice and that, in general, the level of the in vivo macrophage inflammatory response correlated with the level of resistance to Listeria in a given strain. Like resistance to Listeria, the macrophage inflammatory response was found to be genetically controlled by an autosomal, non-H-2-linked gene(s) expressed as incompletely dominant. Backcross analysis showed genetic linkage of the macrophage inflammatory response with resistance to Listeria. Thus, the results of this study provide formal evidence that the cellular basis of the genetically determined, enhanced resistance to Listeria is an augmented pool size of mononuclear phagocytes, and the prompt mobilization of these cells to foci of infection.
D000818:Animals; D001854:Bone Marrow Cells; D002465:Cell Movement; D005260:Female; D008040:Genetic Linkage; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D008088:Listeriosis / Q000235:genetics* / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010529:Peritoneal Cavity / Q000166:cytology; D010586:Phagocytes / Q000276:immunology