Natural resistance to listeriosis: role of host inflammatory responsiveness

The accumulation of inflammatory macrophages at the infective foci appears to represent the major host defense mechanism during the early or innate phase of resistance to infection with Listeria monocytogenes. Certain inbred strains of mice, such as A/J [A] have genetically-determined defects in macrophage mobilization in vivo in response to intraperitoneal (IP) treatment with the nonspecific inflammatory stimulus, thioglycollate. These strains of mice are also genetically-susceptible to infection with Listeria. In contrast, other strains (C57BL/6J or B10.A/SgSn [B]) are high responders for both genetically-determined traits. Linkage analysis of the two traits in backcross progeny showed that the trait of a high macrophage inflammatory response segregates with the trait of resistance to Listeria. These observations suggested that the gene(s) controlling the level of the macrophage inflammatory response is identical with or linked to the gene(s) controlling resistance to Listeria. We have found additional evidence to support this hypothesis by analyzing the expression of the two traits in 12 AXB/BXA recombinant inbred [RI] mouse strains derived from progenitor B (high macrophage response, Listeria-resistant) and A (low macrophage response, Listeria-susceptible) mice. Furthermore, those AXB/BXA strains, which like progenitor A mice, are susceptible to infection with Listeria exhibit a defect in the number of polymorphonuclear leukocytes recovered from peritoneal exudates 18 h after IP injection with thioglycollate. The strain distribution pattern of both the resistance/susceptibility to Listeria and the leukocyte inflammatory response in RI strains is concordant with that of Hc allele coding for effective/defective levels of C5 complement protein.(ABSTRACT TRUNCATED AT 250 WORDS)