Innate immune responses to LCMV infections: natural killer cells and cytokines

Although much remains to be learned, the study of early responses to LCMV infections of mice has contributed to the basic understanding of the regulation of a variety of important innate immune responses. Major discoveries have included the appreciation of the levels of type 1 IFNs induced during endogenous responses to viral infections, the importance of IFN-alpha/beta for induction of NK cell cytotoxicity, and the roles for IFN-alpha/beta in regulating the expression of other innate cytokines, i.e., IL-12 and IFN-gamma produced by NK cells (Fig. 11). Taken together with the characterization of adaptive responses to LCMV, a paradigm is emerging for a possible initial to innate to adaptive response cascade during infections with viruses eliciting endogenous expression of high levels of IFN-alpha/beta. The results not only advance the understanding of endogenous responses to viral infections and how they are balanced to achieve the best possible outcome for the host, but also give insights into possible consequences of therapeutic intervention with type 1 IFNs.