Inflammatory macrophages exploited by oral streptococcus increase IL-1B release via NLRP6 inflammasome.

Chronic inflammatory periodontal disease develops in part from the infiltration of a large number of classically activated inflammatory macrophages that release inflammatory cytokines important for disease progression, including inflammasome-dependent IL-1β. Streptococcus gordonii is a normally commensal oral microorganism; while not causative, recent evidence indicates that commensal oral microbes are required for the full development of periodontal disease. We have recently reported that inflammatory macrophages counterintuitively allow for the increased survival of phagocytosed S. gordonii over non-activated or alternatively activated macrophages. This survival is dependent on increased ROS production within the phagosome of the inflammatory macrophages and resistance by the bacterium and can result in S. gordonii damaging the phagolysosomes. Here we show that activated macrophages infected with live S. gordonii release more IL-1β than macrophages infected with other oral microbes, both classical pathogens and commensals. We also find that S. gordonii dependent inflammatory macrophage inflammasome activation requires the cytoplasmic NLRP6. Overall, our results suggest S. gordonii is capable of evading immune destruction, increasing inflammatory mediators, and increasing inflammatory macrophage response; and that this ability is increased under conditions of inflammation. This work reveals additional mechanisms by which normally commensal oral streptococci-macrophage interactions can change, resulting in increased release of mature IL-1β, potentially contributing to an environment that perpetuates inflammation.