Using a mouse model of pneumonic tularemia, we have recently shown that IL-1 receptor-deficient mice are more susceptible to intranasal infection with Francisella tularensis LVS (Ft). Il-1r1-/- mice were found to have significantly reduced level of IgM specific for Ft LPS. Anti-Ft LPS IgM depended on IL-1β, TLR2, and the inflammasome, promoted bacteria agglutination and phagocytosis, and was protective in passive immunization experiments. Expansion of B1a B cells was significantly decreased in the spleen and peritoneal cavity of infected Il-1b-/- mice, compared to C57BL/6J mice. Adoptive transfer of purified B1a and B1b B cells into Rag-deficient mice indicates that both B1 cell subsets can produce anti-Ft LPS IgM. Caspase-11-deficient mice were also found to be more susceptible to Ft infection because of reduced level of anti-Ft LPS IgM, despite normal levels of IL-1β. Caspase-11 was activated in Ft-infected macrophages and lung epithelial cell lines. Bone marrow reconstitution experiments indicated that caspase-11 activation occurs in a radio-resistant cell type other than the B1 cell, possibly in lung epithelial cells. We are testing the hypothesis that infected lung epithelial cells may undergo caspase-11 pyroptosis, releasing Ft LPS that then becomes available to stimulate B1 cells to produce anti-Ft LPS IgM. Taken together our results identify separate roles for IL-1β and caspase-11 inflammasome for production of pathogen-specific IgM by B1 B cells.