Current understanding of macrophage type 1 cytokine responses during intracellular infections

Abstract

Macrophages are important effector cells in cell-mediated immunity against intracelllular infection. Among cytokines that macrophages are able to release are IL-12 and TNFa. IL-12 is a critical linker between the innate and adaptive cell-mediated immunity, capable of Thl differentiation and IFNy release by T and NK cells. IFNy is critically required for the activation of macrophage bactericidal activities. Recently emerging evidence suggests that macrophages are able to release not only IL-12 and TNFa but also IFNy. However, the mechanisms that control the release of each of these type 1 cytokines in macrophages appear different. While macrophages release TNFa in an indiscriminate and IL- 12-independent way, the release of IL-12, particularly bioactive IL-12 p70, and IFNy is under tight control. We are just beginning to understand what controls the release of IL-12 p70, a question of fundamental importance to understanding the mechanisms underlying the initiation of cell-mediated immunity. Our recent findings have shed more insights into the regulatory mechanisms of macrophage IFNy responses. It has become evident that IL-12 is required not only for Thl differentiation but also for IFNy responses by both T cells and macrophages during intracellular infection. In this overview, we have discussed about the current understanding of the regulation of macrophage type 1 cytokine responses during intracellular infection, based upon the recent findings from us and others.