A schematic representation of pathogen DNA sensing. NTHi internalized as intact bacteria or fragments releases DNA, which can interact with specific pathogen DNA receptors. Toll-like receptor 9, located in endosomes, signals primarily via MyD88 to stimulate NF-κB and cytokine production. DAI can activate IRFs, leading to type I IFN production, via several intermediaries. Pol-III can convert bacterial DNA into dsRNA, also activating IRFs. DNA interaction with AIM2 recruits ASC and procaspase1 to form an inflammasome, leading to caspase1 activation and IL-1/IL-18 maturation.