The Non-receptor Tyrosine Kinase Tec Controls Assembly and Activity of the Noncanonical Caspase-8 Inflammasome

Tec family kinases are intracellular non-receptor tyrosine kinases implicated in numerous functions,including t cell and b cell regulation. however,a role in microbial pathogenesis has not been described. here,we identified tec kinase as a novel key mediator of the inflammatory immune response in macrophages invaded by the human fungal pathogen c. albicans. tec is required for both activation and assembly of the noncanonical caspase-8,but not of the caspase-1 inflammasome,during infections with fungal but not bacterial pathogens,triggering the antifungal response through il-1β. furthermore,we identify dectin-1 as the pathogen recognition receptor being required for syk-dependent tec activation. hence,tec is a novel innate-specific inflammatory kinase,whose genetic ablation or inhibition by small molecule drugs strongly protects mice from fungal sepsis. these data demonstrate a therapeutic potential for tec kinase inhibition to combat invasive microbial infections by attenuating the host inflammatory response. © 2014 zwolanek et al.