Friday, July 26, 2024
7/26/2024
Project Summary The lung is a major target of infections and allergies. Dendritic cells (DCs) in the lung function as sensors of the immune system that detect and process pathogens and allergens to activate T cell-dependent adaptive immunity. In addition, pathogens and allergens often stimulate airway sensory neurons either directly or indirectly, leading to primary defense response such as coughing and sneezing. Recent studies highlighted the role of neurons in immune responses, but the interaction between these two sensor modules, DCs and sensory neurons, in inflammation in the lung is incompletely understood. Infection with helminth parasites is a major health burden worldwide. Some helminth species such as roundworms and hookworms in humans and Nippostrongylus brasiliensis (Nb), a commonly used model agent to study hookworm infection in mice, traffic to the lung during their life cycle and cause potent type 2 inflammation. The larvae of these parasites stay in the lung only transiently before they get coughed up and swallowed to migrate to the intestine, where they eventually mature and lay eggs. Thus, the cough-triggering sensory neurons seem to play an important role in their life cycle, but their role in the regulation of inflammation remains unclear. We previously identified CD301b/Mgl2 as a marker for the migratory type 2 conventional DCs in peripheral organs including the lung, and showed that CD301b+ DCs are required for the differentiation of Th2 cells. We recently found that CD301b+ DCs are required for Nb-induced lung inflammation as well as for timely clearance of the parasite. Interestingly, our data also suggest that CD301b+ DCs and sensory neurons suppress each other to regulate lung inflammation during Nb infection. Based on these data, we hypothesize that Nb parasites are sensed by CD301b+ DCs and sensory neurons, which then mutually regulate each other to orchestrate type 2 inflammation in the lung. By using Nb infection as a model, the long-term goal of this project is to understand how sensory neurons modulate type 2 inflammation in the lung. Since the lung is a major site not only for helminth infection but also for other type 2 inflammation disorders such as allergy, asthma and fibrosis, understanding the mechanism for the regulation of type 2 inflammation is of clinical relevance.
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