Enteric tuft cells coordinate timely expulsion of the tapeworm Hymenolepis diminuta from the murine host by coordinating local but not systemic immunity.

Recognizing that enteric tuft cells can signal the presence of nematode parasites, we investigated whether tuft cells are required for the expulsion of the cestode, Hymenolepis diminuta, from the non-permissive mouse host, and in concomitant anti-helminthic responses. BALB/c and C57BL/6 mice infected with H. diminuta expelled the worms by 11 days post-infection (dpi) and displayed DCLK1+ (doublecortin-like kinase 1) tuft cell hyperplasia in the small intestine (not the colon) at 11 dpi. This tuft cell hyperplasia was dependent on IL-4Rα signalling and adaptive immunity, but not the microbiota. Expulsion of H. diminuta was slowed until at least 14 dpi, but not negated, in tuft cell-deficient Pou2f3-/- mice and was accompanied by delayed goblet cell hyperplasia and slowed small bowel transit. Worm antigen and mitogen evoked production of IL-4 and IL-10 by splenocytes from wild-type and Pou2f3-/- mice was not appreciably different, suggesting similar systemic immune reactivity to infection with H. diminuta. Wild-type and Pou2f3-/- mice infected with H. diminuta displayed partial protection against subsequent infection with the nematode Heligmosomoides bakeri. We speculate that, with respect to H. diminuta, enteric tuft cells are important for local immune events driving the rapidity of H. diminuta expulsion but are not critical in initiating or sustaining systemic Th2 responses that provide concomitant immunity against secondary infection with H. bakeri.

Supporting and Incentivizing Peer Leaders for an Internet-Based Private Peer Community for Youths With Type 1 Diabetes: Social Network and Directed Content Analysis.

BACKGROUND: Youths with type 1 diabetes (T1D) frequently experience stigma. Internet-based peer communities can mitigate this through social support but require leaders to catalyze exchange. Whether nurturing potential leaders translates into a central role has not been well studied. Another issue understudied in such communities is lurking, the viewing of exchanges without commenting or posting. OBJECTIVE: We aimed to assess the centrality of the peer leaders we selected, trained, and incentivized within the Canadian Virtual Peer Network (VPN)-T1D. This is a private Facebook (Meta Platforms, Inc) group that we created for persons aged 14 to 24 years with T1D. We specifically sought to (1) compare a quantitative estimate of network centrality between peer leaders and regular members, (2) assess the proportions of network exchanges that were social support oriented, and (3) assess proportions of high engagement (posts, comments, reactions, and votes) and low engagement (lurking) exchanges. METHODS: We recruited peer leaders and members with T1D from prior study cohorts and clinics. We trained 10 leaders, provided them with a monthly stipend, and encouraged them to post on the private Facebook group we launched on June 21, 2017. We extracted all communications (posts, messages, reactions, polls, votes, and views) that occurred until March 20, 2020. We calculated each member's centrality (80% of higher engagement communications comprising posts, comments, and reactions plus 20% of members with whom they connected). We divided each member's centrality by the highest centrality to compute the relative centrality, and compared the mean values between leaders and members (linear regression). We calculated the proportions of communications that were posts, comments, reactions, and views without reaction. We performed content analysis with a social support framework (informational, emotional, esteem-related, network, and tangible support), applying a maximum of 3 codes per communication. RESULTS: VPN-T1D gained 212 regular members and 10 peer leaders over 33 months; of these 222 members, 26 (11.7%) exited. Peer leaders had 10-fold higher relative centrality than regular members (mean 0.53, SD 0.26 vs mean 0.04, SD 0.05; 0.49 difference; 95% CI 0.44-0.53). Overall, 91.4% (203/222) of the members connected at least once through posts, comments, or reactions. Among the 75,051 communications, there were 5109 (6.81%) posts, comments, and polls, 6233 (8.31%) reactions, and 63,709 (84.9%) views (lurking). Moreover, 54.9% (3430/6253) of codes applied were social support related, 66.4% (2277/3430) of which were informational (eg, insurance and travel preparation), and 20.4% (699/3430) of which were esteem related (eg, relieving blame). CONCLUSIONS: Designating, training, and incentivizing peer leaders may stimulate content exchange and creation. Social support was a key VPN-T1D deliverable. Although lurking accounted for a high proportion of the overall activity, even those demonstrating this type of passive participation likely derived benefits, given that the network exit rate was low. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/18714.