Summary Francisella tularensis, the causative agent of tularemia, infects host macrophages, which triggers production of the proinflammatory cytokines interleukin 1 β (IL-1 β) and IL-18. We elucidate here how host macrophages recognize Francisella and elicit this pro-inflammatory response. Using mice deficient in the DNA-sensing inflammasome component AIM2, we demonstrate here that AIM2 is required for sensing Francisella. AIM2-deficient mice were extremely susceptible to Francisella infection with higher mortality and bacterial burden compared to wild-type mice. Caspase-1, activation, IL-1β secretion and cell death were absent in Aim2−/− macrophages in response to Francisella infection or presence of cytoplasmic DNA. This study identifies AIM2 as a crucial sensor of F. tularensis infection, and provides genetic proof for its critical role in the host innate immunity to intracellular pathogens.

Pardi and colleagues report on a vaccine platform in which purified, antigen-encoding, nucleoside-modified mRNA is encapsulated in lipid nanoparticles. Immunization with this vaccine elicits potent T follicular helper cell, germinal center B cell, and protective, neutralizing antibody responses.

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