Investigating the contributions of hematopoietic stem and progenitor cells to antihelminth immunity and host protection 4301

Abstract Description Protective responses to helminth parasites are dependent on type 2 cytokine-mediated inflammation that is required for worm expulsion and the healing of damaged tissues. These events are critically supported by various cell populations including mast cells. Our previous studies have identified a population of hematopoietic progenitor cells (HPCs) that possess mast cell potential and are defined by their expression of the metabolic enzyme carbonic anhydrase (Car)1. Car1-expressig progenitors exit the bone marrow and traffic to inflamed tissues following a Trichinella spiralis infection. Despite these advances, the relative contributions of Car1-expressing progenitors to the infection-induced increases in mast cells and their contribution to antihelminth immunity remain unknown. To address this, we have developed a novel Car1-ERCre mouse to perform important fate-mapping and lineage deletion studies. Here we demonstrate that our novel mouse model can be used to selectively label Trichinella-induced mast cells with a history of Car1-expression. Furthermore, deleting the Car1-expressing progenitors not only significantly reduced mast cell development, but also resulted in decreased protective immunity in the context of a T. spiralis infection. Collectively, our data suggests that Car1-expressing progenitors critically support infection-induced mast cell responses and represent a therapeutic target for the treatment of mast cell-mediated inflammation. Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)