During the course of an immunizing Listeria monocytogenes infection in mice, all three interferon (IFN) classes (Alpha, Beta, Gamma) are produced. Since IFN preparations, or IFN-producing agents, have been found to afford protection against Listeria infection, it is possible that the Listeria-induced IFNs may function in resistance. To examine this possibility, two experimental approaches will be used to study both acute and chronic models of listeriosis. The first experimental approach will be to use monospecific anti-IFN antibodies to neutralize each endogeneously produced IFN. The second will be to passively administer purified IFNs prior to and at various times during Listeria infection. If an endogeneously produced IFN does play a role in resistance, then its neutralization by specific antibody should result in an exacerbation of infection. Conversely, the administration of an exogenous IFN should enhance resistance. These in vivo studies will establish whether the different IFNs play a role in resistance, and at what phase in the generation or expression of immunity they mediate their function. These studies will also reveal whether exogenous IFN treatment can exert a prophylactic and/or therapeutic effect, and which of the three IFNs exerts the greatest effect. One potential effect of IFNs may be the activation of the listericidal activities of macrophages. The ability of the three IFNs to activate the listericidal actions of three different macrophage populations in vitro will be analyzed. The IFNs may also be capable of inducing a state of anti-Listeria resistance in nonprofessional phagocytes. In this way IFNs could function to suppress the intracellular proliferation of this falcultative intracellular bacterium. This possible antibacterial function of IFNs will be analyzed in vitro, using IFN-treated murine embryo fibroblast cells.
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