Unexpected Roles for Intracellular Complement in the Regulation of Th1 Responses

The complement system is generally recognized as an evolutionarily ancient and critical part of innate immunity required for the removal of pathogens that have breached the protective host barriers. It was originally defined as a liver-derived serum surveillance system that induces the opsonization and killing of invading microbes and amplifies the general inflammatory reactions. However, studies spanning the last four decades have established complement also as a vital bridge between innate and adaptive immunity. Furthermore, recent work on complement, and in particular its impact on human T helper 1 (Th1) responses, has led to the unexpected findings that the complement system also functions within cells and that it participates in the regulation of basic processes of the cell, including metabolism. These recent new insights into the unanticipated noncanonical activities of this ancient system suggest that the functions of complement extend well beyond mere host protection and into cellular physiology.