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      Schistosoma “Eggs-Iting” the Host: Granuloma Formation and Egg Excretion

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          Abstract

          Schistosomiasis is a major cause of morbidity in humans invoked by chronic infection with parasitic trematodes of the genus Schistosoma. Schistosomes have a complex life-cycle involving infections of an aquatic snail intermediate host and a definitive mammalian host. In humans, adult male and female worms lie within the vasculature. Here, they propagate and eggs are laid. These eggs must then be released from the host to continue the life cycle. Schistosoma mansoni and Schistosoma japonicum reside in the mesenteric circulation of the intestines with egg excreted in the feces. In contrast, S. haematobium are present in the venus plexus of the bladder, expelling eggs in the urine. In an impressive case of exploitation of the host immune system, this process of Schistosome “eggs-iting” the host is immune dependent. In this article, we review the formation of the egg granuloma and explore how S. mansoni eggs laid in vasculature must usurp immunity to induce regulated inflammation, to facilitate extravasation through the intestinal wall and to be expelled in the feces. We highlight the roles of immune cell populations, stromal factors, and egg secretions in the process of egg excretion to provide a comprehensive overview of the current state of knowledge regarding a vastly unexplored mechanism.

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          Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit.

          Parasitic helminths and allergens induce a type 2 immune response leading to profound changes in tissue physiology, including hyperplasia of mucus-secreting goblet cells and smooth muscle hypercontractility. This response, known as 'weep and sweep', requires interleukin (IL)-13 production by tissue-resident group 2 innate lymphoid cells (ILC2s) and recruited type 2 helper T cells (TH2 cells). Experiments in mice and humans have demonstrated requirements for the epithelial cytokines IL-33, thymic stromal lymphopoietin (TSLP) and IL-25 in the activation of ILC2s, but the sources and regulation of these signals remain poorly defined. In the small intestine, the epithelium consists of at least five distinct cellular lineages, including the tuft cell, whose function is unclear. Here we show that tuft cells constitutively express IL-25 to sustain ILC2 homeostasis in the resting lamina propria in mice. After helminth infection, tuft-cell-derived IL-25 further activates ILC2s to secrete IL-13, which acts on epithelial crypt progenitors to promote differentiation of tuft and goblet cells, leading to increased frequencies of both. Tuft cells, ILC2s and epithelial progenitors therefore comprise a response circuit that mediates epithelial remodelling associated with type 2 immunity in the small intestine, and perhaps at other mucosal barriers populated by these cells.
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            Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut.

            The intestinal epithelium forms an essential barrier between a host and its microbiota. Protozoa and helminths are members of the gut microbiota of mammals, including humans, yet the many ways that gut epithelial cells orchestrate responses to these eukaryotes remain unclear. Here we show that tuft cells, which are taste-chemosensory epithelial cells, accumulate during parasite colonization and infection. Disruption of chemosensory signaling through the loss of TRMP5 abrogates the expansion of tuft cells, goblet cells, eosinophils, and type 2 innate lymphoid cells during parasite colonization. Tuft cells are the primary source of the parasite-induced cytokine interleukin-25, which indirectly induces tuft cell expansion by promoting interleukin-13 production by innate lymphoid cells. Our results identify intestinal tuft cells as critical sentinels in the gut epithelium that promote type 2 immunity in response to intestinal parasites.
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              WormBase ParaSite − a comprehensive resource for helminth genomics

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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                29 October 2018
                2018
                : 9
                : 2492
                Affiliations
                [1] 1School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin , Dublin, Ireland
                [2] 2National Children's Research Centre, Our Lady's Children's Hospital , Dublin, Ireland
                [3] 3Trinity Translational Medicine Institute, St James's Hospital, Trinity College Dublin , Dublin, Ireland
                Author notes

                Edited by: Thiago Almeida Pereira, Stanford University, United States

                Reviewed by: Fausto Edmundo Lima Pereira, Universidade Vila Velha, Brazil; William Evan Secor, Centers for Disease Control and Prevention (CDC), United States

                *Correspondence: Padraic G. Fallon pfallon@ 123456tcd.ie

                This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology

                †Present Address: Christian Schwartz, IFIZ, Department of Immunology, University of Tübingen, Tübingen, Germany

                Article
                10.3389/fimmu.2018.02492
                6232930
                30459767
                be3d7d8f-8055-4ae7-b01e-183fc55a2f90
                Copyright © 2018 Schwartz and Fallon.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 July 2018
                : 09 October 2018
                Page count
                Figures: 3, Tables: 0, Equations: 0, References: 182, Pages: 16, Words: 13528
                Funding
                Funded by: Science Foundation Ireland 10.13039/501100001602
                Funded by: Wellcome Trust 10.13039/100004440
                Funded by: European Molecular Biology Organization 10.13039/100004410
                Categories
                Immunology
                Review

                Immunology
                schistosoma,inflammation,granuloma,egg,excretion,regulation,intestine,liver
                Immunology
                schistosoma, inflammation, granuloma, egg, excretion, regulation, intestine, liver

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