Cooperation between Adh and OR5M11 contributes to the lung pathogenicity of Actinobacillus pleuropneumoniae by facilitating the NLRP3-mediated inflammatory response.

Actinobacillus pleuropneumoniae (A. pleuropneumoniae) is the etiologic agent of porcine pleuropneumonia, a severe respiratory disease characterized by hemorrhagic, necrotizing lung lesions that cause significant economic losses on the global swine industry. However, the molecular mechanisms underlying the lung pathogenicity of A. pleuropneumoniae remain unclear. Here we demonstrate that A. pleuropneumoniae infection induces lung injury through activating the NLRP3-mediated inflammatory response mediated by the YadA-like head region (Adh) of Apa1, a bacterial adhesin that mediates attachment to host cells. Importantly, we show that Adh triggers the NLRP3-mediated inflammatory response by engaging olfactory receptor family 5 subfamily M member 11 (OR5M11), a host receptor previously shown to interact with Adh. Furthermore, OR5M11 contributes to the Adh-activated inflammatory response by promoting mitochondrial DNA release. Taken together, our results provide new insights into the pathogenesis of A. pleuropneumoniae, particularly regarding NLRP3-mediated inflammatory pathology.