Mucosal mast cells are indispensable for the timely termination of Strongyloides ratti infection

Abstract

Mast cells and basophils are innate immune cells with overlapping functions that contribute to anti-helminth immunity. Mast cell function during helminth infection was previously studied using mast cell-deficient Kit-mutant mice that display additional mast cell-unrelated immune deficiencies. Here, we use mice that lack basophils or mucosal and connective tissue mast cells in a Kit-independent manner to re-evaluate the impact of each cell type during helminth infection. Neither mast cells nor basophils participated in the immune response to tissue-migrating Strongyloides ratti third-stage larvae, but both cell types contributed to the early expulsion of parasitic adults from the intestine. The termination of S. ratti infection required the presence of mucosal mast cells: Cpa3 Cre mice, which lack mucosal and connective tissue mast cells, remained infected for more than 150 days. Mcpt5 Cre R-DTA mice, which lack connective tissue mast cells only, and basophil-deficient Mcpt8 Cre mice terminated the infection after 1 month with wild-Type kinetics despite their initial increase in intestinal parasite burden. Because Cpa3 Cre mice showed intact Th2 polarization and efficiently developed protective immunity after vaccination, we hypothesize that mucosal mast cells are non-redundant terminal effector cells in the intestinal epithelium that execute anti-helminth immunity but do not orchestrate it.