Early consequences of macrophage Francisella tularensis interaction under the influence of different genetic background in mice

The induction, regulation and expression of protective immunity against Francisella tularensis LVS infection is dependent on the results of primary interaction between the cells of host's immunoregulatory system and the microbe. The early events, at least on the side of macrophages, are under the genetic control. To determine the impact of genes that might be involved in the control of resistance to Francisella tularensis LVS infection, vie have used three different inbred strains of mice with increasing resistance to this infection in order C3H/HeJ (Lps(d)), C3H/HeN (Lps(n)), and C57B1/10N (Lps(n)). The controlled production of IL-10, IFN-gamma, and TNF-alpha coupled with increased production of reactive oxygen metabolites during early phase of infection distinguished less susceptible C3H/HeN mice from their more susceptible congenic C3H/HeJ counterparts. The enhancement of oxidative metabolism that appeared on day 5 after the infection of both C3H/HeN and C57B1/10N mice closely correlated with increasing resistance of these two strains of mice to Francisella tularensis LVS infection. These mice were also capable to reach the highest level of TNF-alpha on day 5 after the infection. At the same time interval, only C57B1/10N mice produced significantly enhanced level of nitric oxide. Overall, these parameters may suggest their possible biological role in early-phase resistance to Francisella tularensis LVS infection and their subsequent consequences for ultimate control of infection and its clearance. (C) 1997 Elsevier Science B.V.