Genetic control of resistance to Listeria monocytogenes: regulation of leukocyte inflammatory responses by the Hc locus.
The control mechanisms responsible for the innate resistance of C57BL/6J (B) mice and for the innate susceptibility of A/J (A) mice to infection with Listeria monocytogenes were studied by typing the recombinant inbred (RI) strains derived from these two progenitors for the trait of Listeria resistance/susceptibility. The strain distribution pattern (SDP) of this trait obtained in the 13 AXB/BXA RI strains studied suggests that an allelic difference at a major locus (Lr-1) is responsible for the trait of resistance/susceptibility to Listeria. In addition, another putative gene (Lr-2) unlinked to Lr-1 is postulated to control the level of bacterial load within the group of susceptible strains. The SDP of A and B alleles at the Lr-1 locus was fully concordant with that observed for the Hc locus (controlling the level of the C5 component of complement). This suggests that the genetic susceptibility of A strains of mice to Listeria infection is either directly due to or related to the C5 deficiency found in that strain. This conclusion is enhanced by the observation of a significant protection of A mice from listeriosis by the infusion of C5-rich serum. A survey of RI strains for the magnitude of PMN and macrophage inflammatory responses showed that the expression of both traits co-segregated and that the C5 deficiency was the major factor responsible for the defective inflammatory response of A strain mice. We conclude that a defect in the phagocyte inflammatory responses caused by C5 deficiency is the major reason for the extreme susceptibility of A mice to Listeria.
D000818:Animals; D003182:Complement C5 / Q000502:physiology; D004198:Disease Susceptibility; D008040:Genetic Linkage; D006461:Hemolysis; D007113:Immunity, Innate; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000628:therapy; D008088:Listeriosis / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000502:physiology; D010641:Phenotype; D013045:Species Specificity
D003182:Complement C5