Trichinella spiralis-induced mastocytosis and erythropoiesis are simultaneously supported by a bipotent mast cell/erythrocyte precursor cell.

Anti-helminth responses require robust type 2 cytokine production that simultaneously promotes worm expulsion and initiates the resolution of helminth-induced wounds and hemorrhaging. However, how infection-induced changes in hematopoiesis contribute to these seemingly distinct processes remains unknown. Recent studies have suggested the existence of a hematopoietic progenitor with dual mast cell-erythrocyte potential. Nonetheless, whether and how these progenitors contribute to host protection during an active infection remains to be defined. Here, we employed single cell RNA-sequencing and identified that the metabolic enzyme, carbonic anhydrase (Car) 1 marks a predefined bone marrow-resident hematopoietic progenitor cell (HPC) population. Next, we generated a Car1-reporter mouse model and found that Car1-GFP positive progenitors represent bipotent mast cell/erythrocyte precursors. Finally, we show that Car1-expressing HPCs simultaneously support mast cell and erythrocyte responses during Trichinella spiralis infection. Collectively, these data suggest that mast cell/erythrocyte precursors are mobilized to promote type 2 cytokine responses and alleviate helminth-induced blood loss, developmentally linking these processes. Collectively, these studies reveal unappreciated hematopoietic events initiated by the host to combat helminth parasites and provide insight into the evolutionary pressure that may have shaped the developmental relationship between mast cells and erythrocytes. Author summary Helminth parasites infect approximately 2 billion people and represent a significant public health concern. Helminths undertake complex developmental life cycles through multiple organs and as a result cause substantial tissue damage. To combat this, mammals have evolved mechanisms to initiate balanced immune responses that promote inflammation needed to seclude parasites in granulomas, reduce parasitic burdens and mitigate the consequences of helminth-induced wounds. Despite their clinical importance, the mechanisms that regulate these events remain poorly defined. Here we have uncovered a unique progenitor cell that supports both proinflammatory mast cell responses and red blood cell development, thereby simultaneously initiating both of these host-protective responses. Collectively, these studies reveal unappreciated events initiated by the host to combat pathogens that infect billions of individuals worldwide.