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      Helminths in the gastrointestinal tract as modulators of immunity and pathology

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          Abstract

          Helminth parasites are highly prevalent in many low- and middle-income countries, in which inflammatory bowel disease and other immunopathologies are less frequent than in the developed world. Many of the most common helminths establish themselves in the gastrointestinal tract and can exert counter-inflammatory influences on the host immune system. For these reasons, interest has arisen as to how parasites may ameliorate intestinal inflammation and whether these organisms, or products they release, could offer future therapies for immune disorders. In this review, we discuss interactions between helminth parasites and the mucosal immune system, as well as the progress being made toward identifying mechanisms and molecular mediators through which it may be possible to attenuate pathology in the intestinal tract.

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          Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity.

          Monocyte differentiation into macrophages represents a cornerstone process for host defense. Concomitantly, immunological imprinting of either tolerance or trained immunity determines the functional fate of macrophages and susceptibility to secondary infections. We characterized the transcriptomes and epigenomes in four primary cell types: monocytes and in vitro-differentiated naïve, tolerized, and trained macrophages. Inflammatory and metabolic pathways were modulated in macrophages, including decreased inflammasome activation, and we identified pathways functionally implicated in trained immunity. β-glucan training elicits an exclusive epigenetic signature, revealing a complex network of enhancers and promoters. Analysis of transcription factor motifs in deoxyribonuclease I hypersensitive sites at cell-type-specific epigenetic loci unveiled differentiation and treatment-specific repertoires. Altogether, we provide a resource to understand the epigenetic changes that underlie innate immunity in humans. Copyright © 2014, American Association for the Advancement of Science.
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            Transforming growth factor-beta regulation of immune responses.

            Transforming growth factor-beta (TGF-beta) is a potent regulatory cytokine with diverse effects on hemopoietic cells. The pivotal function of TGF-beta in the immune system is to maintain tolerance via the regulation of lymphocyte proliferation, differentiation, and survival. In addition, TGF-beta controls the initiation and resolution of inflammatory responses through the regulation of chemotaxis, activation, and survival of lymphocytes, natural killer cells, dendritic cells, macrophages, mast cells, and granulocytes. The regulatory activity of TGF-beta is modulated by the cell differentiation state and by the presence of inflammatory cytokines and costimulatory molecules. Collectively, TGF-beta inhibits the development of immunopathology to self or nonharmful antigens without compromising immune responses to pathogens. This review highlights the findings that have advanced our understanding of TGF-beta in the immune system and in disease.
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              Control of neglected tropical diseases.

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                Author and article information

                Journal
                Am J Physiol Gastrointest Liver Physiol
                Am. J. Physiol. Gastrointest. Liver Physiol
                ajpgi
                ajpgi
                AJPGI
                American Journal of Physiology - Gastrointestinal and Liver Physiology
                American Physiological Society (Bethesda, MD )
                0193-1857
                1522-1547
                1 June 2017
                16 March 2017
                16 March 2017
                : 312
                : 6
                : G537-G549
                Affiliations
                [1] 1Wellcome Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow , Glasgow, United Kingdom;
                [2] 2Edinburgh Clinical Academic Track, Western General Hospital, University of Edinburgh , Edinburgh, United Kingdom; and
                [3] 3Department of Neurology, University of Wisconsin School of Medicine and Public Health , Madison, Wisconsin
                Author notes
                Address for reprint requests and other correspondence: R. M. Maizels, Wellcome Centre for Molecular Parasitology, Inst. of Infection, Immunity and Inflammation, Univ. of Glasgow, 120 University Pl., Glasgow G12 8TA, UK (e-mail: rick.maizels@ 123456glasgow.ac.uk ).
                Article
                GI-00024-2017 GI-00024-2017
                10.1152/ajpgi.00024.2017
                5495915
                28302598
                0e715ad0-7b1e-4b5a-8e99-60a9fec951ea
                Copyright © 2017 the American Physiological Society

                Licensed under Creative Commons Attribution CC-BY 4.0: © the American Physiological Society.

                History
                : 18 January 2017
                : 6 March 2017
                : 12 March 2017
                Funding
                Funded by: http://doi.org/10.13039/100004440 Wellcome Trust
                Award ID: 106122
                Award ID: 104111
                Funded by: http://doi.org/10.13039/100000890 National Multiple Sclerosis Society
                Award ID: RG 3613A4/1
                Categories
                Review
                Inflammation, Immunity, Fibrosis, and Infection

                Anatomy & Physiology
                Anatomy & Physiology

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