| Summary: | <i>Brucella abortus</i> is a zoonotic pathogen that causes brucellosis. Because of <i>Brucella’s</i> unique LPS layer and intracellular localization predominately within macrophages, it can often evade immune detection. However, pattern recognition receptors are capable of sensing <i>Brucella</i> pathogen-associated molecular patterns (PAMPS). For example, NOD-like receptors (NLRs) can form a multi-protein inflammasome complex to attenuate <i>Brucella</i> pathogenesis. The inflammasome activates IL-1β and IL-18 to drive immune cell recruitment. Alternatively, inflammasome activation also initiates inflammatory cell death, termed pyroptosis, which augments bacteria clearance. In this report, we assess canonical and non-canonical inflammasome activation following <i>B. abortus</i> infection. We conducted <i>in vivo</i> studies using <i>Asc<sup>-/-</sup></i> mice and observed decreased mouse survival, immune cell recruitment, and increased bacteria load. We also conducted studies with <i>Caspase-11<sup>-/-</sup></i> mice and did not observe any significant impact on <i>B. abortus</i> pathogenesis. Through mechanistic studies using <i>Asc<sup>-/-</sup></i> macrophages, our data suggests that the protective role of ASC may result from the induction of pyroptosis through a gasdermin D-dependent mechanism in macrophages. Additionally, we show that the recognition of <i>Brucella</i> is facilitated by sensing the PAMP gDNA rather than the less immunogenic LPS. Together, these results refine our understanding of the role that inflammasome activation and pyroptosis plays during brucellosis.
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