Current understanding of macrophage type 1 cytokine responses during intracellular infections.
Macrophages are important effector cells in cell-mediated immunity against intracellular infection. Among cytokines that macrophages are able to release are IL-12 and TNF alpha. IL-12 is a critical linker between the innate and adaptive cell-mediated immunity, capable of Th1 differentiation and IFN gamma release by T and NK cells. IFN gamma 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 TNF alpha but also IFN gamma. However, the mechanisms that control the release of each of these type 1 cytokines in macrophages appear different. While macrophages release TNF alpha in an indiscriminate and IL-12-independent way, the release of IL-12, particularly bioactive IL-12 p70, and IFN gamma 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 IFN gamma responses. It has become evident that IL-12 is required not only for Th1 differentiation but also for IFN gamma 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.
Xing
Z
Z
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada. xingz@fhs.csu.mcmaster.ca
D000818:Animals; D016207:Cytokines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D009164:Mycobacterium Infections / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines