Vasoactive intestinal peptide promotes host defense against enteric pathogens by modulating the recruitment of group 3 innate lymphoid cells.

Group 3 innate lymphoid cells (ILC3s) control the formation of intestinal lymphoid tissues and play key roles in intestinal defense. They express neuropeptide vasoactive intestinal peptide (VIP) receptor 2 (VPAC2), through which VIP modulates their function, but whether VIP exerts other effects on ILC3 remains unclear. We show that VIP promotes ILC3 recruitment to the intestine through VPAC1 independent of the microbiota or adaptive immunity. VIP is also required for postnatal formation of lymphoid tissues as well as the maintenance of local populations of retinoic acid (RA)-producing dendritic cells, with RA up-regulating gut-homing receptor CCR9 expression by ILC3s. Correspondingly, mice deficient in VIP or VPAC1 suffer a paucity of intestinal ILC3s along with impaired production of the cytokine IL-22, rendering them highly susceptible to the enteric pathogen Citrobacter rodentium This heightened susceptibility to C. rodentium infection was ameliorated by RA supplementation, adoptive transfer of ILC3s, or by recombinant IL-22. Thus, VIP regulates the recruitment of intestinal ILC3s and formation of postnatal intestinal lymphoid tissues, offering protection against enteric pathogens.

Perspectives of People with Multiple Sclerosis About Helminth Immunotherapy.

BACKGROUND: Due to the chronic and incurable nature of the autoimmune disease multiple sclerosis (MS), some people with MS will seek out alternative therapeutic approaches. Helminth immunotherapy, the deliberate inoculation with helminthic parasites as an intervention to prevent, delay, or minimize progression of autoimmune disorders, is one such approach gaining traction in academic research and with the public. Herein, we explored the perspectives of people with MS regarding helminth immunotherapy and its use in disease management. METHODS: Interpretive description, a qualitative research approach, was applied to data extracted from online forums. Multiple investigators independently identified, extracted, and analyzed data to develop preliminary codes. Inductive thematic analysis and triangulation were then used to collaboratively establish themes. RESULTS: Four main themes were generated: experience of living with MS, influential factors in contemplating helminth immunotherapy, logistics of helminth immunotherapy, and concerns about helminth immunotherapy. CONCLUSIONS: There was a general consensus in publicly available online forums that conventional therapies do not provide meaningful improvement for some people with MS. These people may seek alternative therapies such as helminth immunotherapy. Information on helminth immunotherapy from internet resources (eg, blogs and social media forums) can contain biased and scientifically unsupported opinions. Messages of efficacy and improved quality of life are readily available and may influence people with MS considering helminth immunotherapy as an alternative therapy. Although some people with MS are seeking helminth immunotherapy, clinical trial data do not currently support its use for people with MS.

The Multibiome: The Intestinal Ecosystem's Influence on Immune Homeostasis, Health, and Disease.

Mammalian evolution has occurred in the presence of mutualistic, commensal, and pathogenic micro- and macro-organisms for millennia. The presence of these organisms during mammalian evolution has allowed for intimate crosstalk between these colonizing species and the host immune system. In this review, we introduce the concept of the 'multibiome' to holistically refer to the biodiverse collection of bacteria, viruses, fungi and multicellular helminthic worms colonizing the mammalian intestine. Furthermore, we discuss new insights into multibiome-host interactions in the context of host-protective immunity and immune-mediated diseases, including inflammatory bowel disease and multiple sclerosis. Finally, we provide reasons to account for the multibiome in experimental design, analysis and in therapeutic applications.