Detecting DNA: An Overview of DNA Recognition by Inflammasomes and Protection against Bacterial Respiratory Infections

The innate immune system plays a key role in modulating host immune defense during bacterial disease. Upon sensing pathogen-associated molecular patterns (PAMPs), the multi-protein complex known as the inflammasome serves a protective role against bacteria burden through facilitating pathogen clearance and bacteria lysis. This can occur through two mechanisms: (1) the cleavage of pro-inflammatory cytokines IL-1β/IL-18 and (2) the initiation of inflammatory cell death termed pyroptosis. In recent literature, AIM2-like Receptor (ALR) and Nod-like Receptor (NLR) inflammasome activation has been implicated in host protection following recognition of bacterial DNA. Here, we review current literature synthesizing mechanisms of DNA recognition by inflammasomes during bacterial respiratory disease. This process can occur through direct sensing of DNA or indirectly by sensing pathogen-associated intracellular changes. Additionally, DNA recognition may be assisted through inflammasome–inflammasome interactions, specifically non-canonical inflammasome activation of NLRP3, and crosstalk with the interferon-inducible DNA sensors Stimulator of Interferon Genes (STING) and Z-DNA Binding Protein-1 (ZBP1). Ultimately, bacterial DNA sensing by inflammasomes is highly protective during respiratory disease, emphasizing the importance of inflammasome involvement in the respiratory tract.