EARLY CONSEQUENCES OF MACROPHAGE FRANCISELLA-TULARENSIS INTERACTION UNDER THE INFLUENCE OF DIFFERENT GENETIC BACKGROUND IN MICE

The induction, regulation and expression of protective immunity agains t Francisella tularensis LVS infection is dependent on the results of primary interaction between the cells of host's immunoregulatory syste m and the microbe. The early events, at least on the side of macrophag es, are under the genetic control. To determine the impact of genes th at might be involved in the control of resistance to Francisella tular ensis LVS infection, vie have used three different inbred strains of m ice with increasing resistance to this infection in order C3H/HeJ (Lps (d)), C3H/HeN (Lps(n)), and C57B1/10N (Lps(n)). The controlled product ion of IL-10, IFN-gamma, and TNF-alpha coupled with increased producti on of reactive oxygen metabolites during early phase of infection dist inguished less susceptible C3H/HeN mice from their more susceptible co ngenic C3H/HeJ counterparts. The enhancement of oxidative metabolism t hat appeared on day 5 after the infection of both C3H/HeN and C57B1/10 N mice closely correlated with increasing resistance of these two stra ins of mice to Francisella tularensis LVS infection. These mice were a lso 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 si gnificantly enhanced level of nitric oxide. Overall, these parameters may suggest their possible biological role in early-phase resistance t o Francisella tularensis LVS infection and their subsequent consequenc es for ultimate control of infection and its clearance. (C) 1997 Elsev ier Science B.V.