Unravelling the cellular sources and location of IL-17A production during a Giardia infection

IL-17A plays a crucial role in the immune defense against Giardia infection, yet its cellular sources remain incompletely defined. In this study, the site-specific expression and cellular origin of IL-17A were investigated, focusing on both adaptive and innate immune cells in the small intestine, Peyer's patches and mesenteric lymph nodes of Giardia muris infected C57BL/6 mice. RT-qPCR analyses showed that IL-17A mRNA expression was significantly upregulated in the small intestine, slightly elevated in the Peyer's patches and unchanged in the mesenteric lymph nodes. Flow cytometry revealed that CD4⁺ T helper cells in the lamina propria of the small intestine are the predominant source of anti-giardial IL-17A. No increase in IL-17A was detected by γδT cells, Tc cells, NK(T) cells, B cells, neutrophils, dendritic cells and innate lymphoid cells. Within the CD3^- innate cell population, increased IL-17A production was observed in MHC-II⁺CD11c⁺CD11b^+/- cells, including a subset of cells expressing typical macrophage markers, namely MHC-II⁺CD11c⁺CD11b⁺CD64⁺F4/80⁺ cells. In T cell-deficient mice, both IL-17A expression and parasite clearance were severely impaired. Our findings demonstrate the importance of the adaptive immunity and simultaneously identify Th cells in the lamina propria as the main source of anti-giardial IL-17A, with a possible supporting role from macrophage-like antigen-presenting cells.