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Background Tuft cells are a rare chemosensory population of the intestinal epithelium that detect intestinal parasitic nematodes and release IL-25 to mobilize innate lymphoid type 2 cells (ILC2), which then drive a Th2- dominant nematode expulsion response. Immunocompetent mice develop tuft cell hyperplasia in the small intestine during infection with Hymenolepis diminuta, a non-abrasive lumen dwelling small intestinal cestode parasite. Helminth infections are accompanied by alterations in sensory motor functions of the gut as well as the composition of the microbiota. It is poorly understood if tuft cell hyperplasia is regulated by these immunomodulatory influences. Aims To test if mice lacking (1) a functional adaptive immune system, (2) TRPV1+ gut-innervating sensory nerves and (3) a microbiome, display enteric tuft cell hyperplasia following infection with H. diminuta. Methods RAG-1-/- (male and female) and germ-free mice (n=3–6) were infected with 5 cysticercoids of H. diminuta and age matched non-infected mice served as control groups. Male C57BL/6j mice were treated with resiniferatoxin (RTX) to ablate TRPV1 +sensory neurons before infection. Mid-jejunum cryostat or paraffin embedded sections immunostained against doublecortin-like kinase -1 (DCLK-1) were blindly scored for tuft cell enumeration at 5–14 days post-infection. Results Tuft cell hyperplasia (~10-15-fold increase) was observed in the jejunum of wild-type mice at 11 days post infection with H. diminuta, by which time worms are expelled. Infected RAG-1-/- mice develop tuft cell hyperplasia of lesser magnitude than wild-type mice. Germ-free mice displayed tuft cell hyperplasia and kinetics of worm expulsion that were not different from wild-type mice. RTX-treated mice with confirmed loss of TRPV1+ nerve fibers in the gut and their cell soma in the dorsal root and nodose ganglia, had a greater increase (~2-fold) in tuft cell numbers compared to H. diminuta-only mice at 11 days post-infection. Conclusions Knowledge of how the host senses helminths in the gut lumen is central to the host-parasite interaction. Using the H. diminuta-mouse model system we find that tuft cell hyperplasia is largely, but not entirely dependent on adaptive immunity, occurs independent of the gut microbiota, and, intriguingly, TRPV1+ sensory nerves appear to act as a brake on the system, limiting the magnitude of the hyperplasia. Funding Agencies CIHRNSERC, Henry Koopman’s Memorial scholarship

A47 ENTERIC TUFT CELL HYPERPLASIA FOLLOWING INFECTION WITH THE TAPEWORM HYMENOLEPIS DIMINUTA IS AFFECTED BY NEURONAL BUT NOT BACTERIAL FACTORS