A negative regulator or just an unconcerned passerby: phosphoinositide 3-kinase signalling in IL-12 production

Pathogens are eliminated from the host by the cooperative functions of the innate and adaptive immune systems, where interleukin 12 (IL-12) plays a crucial role. As overactivity of IL-12 can lead to autoimmune-mediated tissue damage, IL-12 production is tightly regulated. Notably, the phosphoinositide 3-kinase (PI3K) pathway suppresses Toll-like receptor (TLR)-induced IL-12 production as an auto-inhibitory regulator in dendritic cells. However, Okazaki et al. (C5a controls TLR-induced IL-10 and IL-12 production independent of phosphoinositide 3-kinase. J. Biochem. 2011;149:265-274) recently indicated that PI3K activated downstream of C5a anaphylatoxin does not affect the induction of IL-12 by TLR, although C5a efficiently inhibits the induction, in macrophages. PI3K is thus a context-dependent regulator of TLR-mediated IL-12 production.