A232 TUFT CELLS COORDINATE RAPID EXPULSION OF THE TAPEWORM <i>H. DIMINUTA</i> BUT ARE NOT REQUIRED FOR ENHANCED IMMUNITY AGAINST THE NEMATODE, <i>H. POLYGYRUS,</i> IN MICE PREVIOUSLY INFECTED WITH <i>H. DIMINUTA</i>

Abstract Background The tuft cell is an important sentinel that monitors the gut lumen and coordinates immunity against parasitic nematodes. We showed small intestinal tuft cell hyperplasia 11 days post-infection (dpi.) with the tapeworm Hymenolepis diminuta: a time when the parasite is no longer present in murine hosts. This may be a way by which the host protects itself from subsequent helminth-infections, a common phenomenon in parasite-endemic world regions. We test this supposition using Pou2f3-/- mice that lack tuft cells. Aims To test the hypothesis that tuft cells are important in the anti-worm response in H. diminuta ( H.d.)-infected mice subsequently infected with the nematode parasite Heligosomoides polygyrus ( H.p.). Methods Male C57BL6 and Pou2f3-/- mice (8–12 weeks) were infected with 5 H.d. cysticercoids ± 200 H.p. larvae at 10 dpi with H. diminuta (non H.p. mice - control). Upon necropsy at 24 dpi H. diminuta (i.e. 14 dpi H.p. in co-infected mice), both worms were ennumerated in small intestinal washings, H.p. granulomas examined and fecal egg counts performed. Small intestinal segments were stained for tuft (DCLK1+) and goblet cells (PAS+). As a surrogate of successful infection, IL-4 and IL-10 were measured in supernatants from concanavalin-A treated splenocytes. Results Wild-type (WT) mice expel H. diminuta by 11 dpi and this was delayed in Pou2f3-/-mice, with worms readily detectable at 14 dpi and absent by 21 dpi. Despite the delayed expulsion, both WT and Pou2f3-/- mice showed increased splenic production of IL-4 and IL-10; however, unlike WT mice, H. diminuta-infected Pou2f3-/- mice show no increase in jejunal goblet cell numbers. Mice infected with H. diminuta displayed a degree of increased resistance to H.p.-infection defined by reduced worm and egg burdens, and increased granuloma formation in comparison to H.p.-only infected animals. In this sequential co-infection model, there were no significant differences between WT and Pou2f3-/- mice in the response to H.p. Conclusions The absence of tuft cells slows expulsion of H. diminuta from its non-permissive mouse host and correlates with diminished goblet cell hyperplasia. Hypothesizing that H. diminuta-evoked tuft cell hyperplasia would enhance the immune response to a subsequent infection with an unrelated nematode parasite proved incorrect. While H. diminuta-infected mice were partially protected from H.p., response was similar in WT and Pou2f3-/- mice. Thus tuft cells are important in worm detection: yet, our co-infection data suggests that other events initiated by the primary worm infection impact the outcome of subsequent infection with a different helminth and tuft cells have a limited, if any, role to play in this helminth-host-helminth interaction. Funding Agencies CIHRNSERC, Eye’s High International doctoral scholarship

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