SR-B1 Is a Silica Receptor that Mediates Canonical Inflammasome Activation

The inhalation of silica dust is associated with fibrosis and lung cancer, which are triggered by macrophage inflammatory responses; however, how macrophages recognize silica remains largely unknown. Here, we identify by functional expression cloning the class B scavenger receptor SR-B1 as a silica receptor. Through an extracellular α-helix, both mouse and human SR-B1 specifically recognized amorphous and crystalline silica, but not titanium dioxide nanoparticles, latex nanoparticles, or monosodium urate crystals, although all particles exhibited negative surface potentials. Genetic deletion of SR-B1 and masking of SR-B1 by monoclonal antibodies showed that SR-B1-mediated recognition of silica is associated with caspase-1-mediated inflammatory responses in mouse macrophages and human peripheral blood monocytes. Furthermore, SR-B1 was involved in silica-induced pulmonary inflammation in mice. These results indicate that SR-B1 is a silica receptor associated with canonical inflammasome activation. [Display omitted] •Mouse and human SR-B1 recognize silica but not TiO2 or MSU crystals•Silica binds an extracellular alpha helix of SR-B1•SR-B1-mediated tethering and internalization of silica activates inflammasomes•SR-B1 mediates silica-induced lung inflammation Recognition of silica by macrophages causes inflammation associated with fibrosis and cancer, but how macrophages recognize silica remains unclear. Tsugita et al. now identify SR-B1 as a silica receptor that mediates canonical inflammasome activation and subsequent lung inflammation.