NOD1 signaling regulates early tissue inflammation during helminth infection.

The role of innate receptors in initiating the early inflammatory response to helminth larval stages in affected tissues during their life cycle within the host remains poorly understood. Given its pivotal role in detecting microbial elements and eliciting immune responses, exploring the NOD1 receptor could offer crucial insights into immune responses to parasitic infections. By using the larval ascariasis model, the acute model for early Ascaris sp. infection in humans, we report that NOD1 signaling markedly regulates pulmonary tissue inflammation during Ascaris larval migration. Here we show that Ascaris-infected NOD1-deficient mice exhibited a pronounced decrease in macrophage and eosinophil recruitment to the lungs. This diminished cellular recruitment to the lung correlated with impaired production of a mixed cytokine profile including IFN-γ, IL-1β, IL-5, IL-10, IL-17 and IL-33. The attenuated inflammatory response observed in the absence of NOD1 signaling during infection was associated with a notable amelioration in lung dysfunction compared to WT-infected mice. Systemically, NOD1 signaling was also associated with Ascaris-specific IgG2b antibody responses. In summary, our findings highlight a pathogenic role for NOD1 signaling in Ascaris-induced tissue inflammation, underlying hematopoietic cell recruitment and regulating downstream inflammatory cascades associated with the host's innate immune responses in the tissue triggered by helminth larval migration.