The role of the intracellular complement system - the complosome - in monocytes

National Heart, Lung, And Blood Institute

Investigators

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Abstract

Our laboratory has identified a novel role for intracellular complement activity in the regulation of human T cell responses. In collaboration with groups from within the NIH and international collaborators, we have now extended this finding and defined a role for the intracellular C5ar1 also in normal human and mouse monocyte biology. Intracellular C5aR1 signaling on mitochondria is required for optimal IL-1beta production during infection but also sterile inflammation. We have assessed the in vivo biological significance of this observation using appropriate infection (candida) and CVD mouse models and noted that intracellular C5aR1 activity in macrophages contributes to CVD in mice and humans (manuscript under review). We are also testing currently the effects of cell-permeable C3 inhibitors in vitro with an eye on the development of preclinical models. The work has progressed and is nearing publication (manuscript under revision).