6 billion people are currently infected with parasitic worms. Group 2 innate lymphoid cells (ILC2) play a central role in promoting the protective type 2 immunity against these parasites. Here we show that a subpopulation of intestinal ILC2 express the immune checkpoint molecule CD160 in mice infected with the parasitic nematode Strongyloides ratti. CD160+ ILC2 represented a distinct ST2-IL-17RB+Ki-67+ subset that expanded in vivo during S. ratti infection. By contrast, CD160- ILC2 were ST2+IL-17RB-Ki-67- and represented the dominant producers of type 2 cytokines. Upon in vitro stimulation, sorted CD160+ ILC2 progressively lost CD160 expression and acquired cytokine-producing capacity. While CD160-competent RAG KO mice efficiently controlled S. ratti infection with less than 1% of the infective dose remaining by day 10 post-infection, CD160-deficient RAG KO mice failed to expand intestinal ILC2, failed to activate mucosal mast cells and retained high intestinal worm burden for nearly 100 days. Adoptive transfer of CD160-competent ILC2 into S. ratti-infected CD160-deficient RAG KO mice partially restored mast cell activation and reduced intestinal worm burden by 50%. Collectively, these findings identify CD160 expression as a critical checkpoint in the development and expansion of fully functional ILC2 required for effective immunity against intestinal helminth infection.
Heepmann et al. (Wed,) studied this question.