Dynamics of Interleukin-9 Producing Lymphocytes in Strongyloides ratti-Infected Mice

Helminths infect a quarter of the human population and are controlled in the frame of a canonical type-2 immune response. Interleukin-9 is a cytokine with pleiotropic functions during type-2 immunity that can be produced by many different cells. Accumulating evidence suggest that IL-9 is of particular relevance in controlling intestinal helminth infections. Using mice infected with the parasitic nematode Strongyloides ratti, we showed previously that ejection from the intestine depends on IL-9 and IL-9-mediated activation of mucosal mast cells. Here we use IL-9 reporter mice to identify the relevant cellular sources of IL-9 in vivo. We report that predominantly CD4⁺ T cells and group 2 innate lymphoid cells (ILC2s) produced IL-9 in S. ratti-infected or IL-33-treated mice. Interestingly, the IL-33-mediated induction of IL-9 and subsequent mast cell degranulation was modulated by concurrent S. ratti infection. While the IL-33-mediated expansion of IL-9-producing ILC2s was supressed by S. ratti infection, IL-9-producing CD4⁺ T cells were proportionally increased. Finally, we show that S. ratti-derived E/S products interfered with IL-9 production by BM-derived ILC2 in vitro. In conclusion, we have identified that ILC2 and CD4⁺ T cells produce IL-9 during S. ratti infection, and that ILC2 responses are suppressed by S. ratti products.