In addition to infecting intestinal epithelial cells, Shigella infect macrophages within the intestinal lamina propria and Peyer’s patches. Macrophages are both activated and killed by intracellular Shigella. Macrophage are activated by recognition of lipopolysaccharide (LPS) from gram-negative bacteria. LPS recognition activates inflammasomes in the macrophage cytosol, which triggers the release of pro-inflammatory cytokines and inflammatory cell death. We discovered that the human protein NLRP11 is a pattern recognition receptor for bacterial LPS in the cytosol of macrophages (Sci Immunol, 2023, 10.1126/sciimmunol.abo4767). Using cell biology, protein biochemistry, and primary and cell culture-based assays, we are working to uncover the mechanisms of NLRP11 function and the scope of its contribution to innate immune responses.