The MUC1 mucin specifically inhibits activation of the NLRP3 inflammasome.

MUC1 is a cell membrane-associated mucin, expressed ubiquitously on the mucosal epithelia as well as by immune cells, that limits the inflammatory response to multiple pathogens. We have recently shown that MUC1 controls inflammation resulting from Helicobacter pylori infection by suppressing interleukin-1β (IL-1β) produced via the NLRP3 inflammasome. Here, we demonstrate that MUC1 also regulates IL-1β secretion induced by the NLRP3-activating bacteria Haemophilus influenzae but not bacteria that activate other inflammasomes. Using purified ligands, we further demonstrate that MUC1 regulation of NLRP3 is specific, as it has no effect on the NLRP1b, NLRC4 and AIM2 inflammasomes. This indicates a unique role for MUC1 in the regulation of NLRP3-activating bacterial infections.