ASC-Mediated Inflammation and Pyroptosis Attenuates Pathogenesis Following the Recognition of GDNA

is a zoonotic pathogen that causes brucellosis. Because of unique LPS layer and intracellular localization predominately within macrophages, it can often evade immune detection. However, pattern recognition receptors are capable of sensing pathogen-associated molecular patterns (PAMPS). For example, NOD-like receptors (NLRs) can form a multi-protein inflammasome complex to attenuate 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 infection. We conducted in vivo studies using mice and observed decreased mouse survival, immune cell recruitment, and increased bacteria load. We also conducted studies with mice and did not observe any significant impact on pathogenesis. Through mechanistic studies using 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 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.