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      Immunity to gastrointestinal nematodes: mechanisms and myths

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          Abstract

          Immune responses to gastrointestinal nematodes have been studied extensively for over 80 years and intensively investigated over the last 30–40 years. The use of laboratory models has led to the discovery of new mechanisms of protective immunity and made major contributions to our fundamental understanding of both innate and adaptive responses. In addition to host protection, it is clear that immunoregulatory processes are common in infected individuals and resistance often operates alongside modulation of immunity. This review aims to discuss the recent discoveries in both host protection and immunoregulation against gastrointestinal nematodes, placing the data in context of the specific life cycles imposed by the different parasites studied and the future challenges of considering the mucosal/immune axis to encompass host, parasite, and microbiome in its widest sense.

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          Local macrophage proliferation, rather than recruitment from the blood, is a signature of TH2 inflammation.

          S J Jenkins, D. Rückerl, P. C. Cook … (2011)
          A defining feature of inflammation is the accumulation of innate immune cells in the tissue that are thought to be recruited from the blood. We reveal that a distinct process exists in which tissue macrophages undergo rapid in situ proliferation in order to increase population density. This inflammatory mechanism occurred during T helper 2 (T(H)2)-related pathologies under the control of the archetypal T(H)2 cytokine interleukin-4 (IL-4) and was a fundamental component of T(H)2 inflammation because exogenous IL-4 was sufficient to drive accumulation of tissue macrophages through self-renewal. Thus, expansion of innate cells necessary for pathogen control or wound repair can occur without recruitment of potentially tissue-destructive inflammatory cells.
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            Type 2 innate lymphoid cells control eosinophil homeostasis

            Jesse C. Nussbaum, Steven Van Dyken, Jakob von Moltke … (2013)
            Eosinophils are specialized myeloid cells associated with allergy and helminth infections. Blood eosinophils demonstrate circadian cycling, as described over 80 years ago, 1 and are abundant in the healthy gastrointestinal tract. Although a cytokine, interleukin (IL)-5, and chemokines such as eotaxins, mediate eosinophil development and survival, 2 and tissue recruitment, 3 respectively, the processes underlying the basal regulation of these signals remain unknown. Here, we show that serum IL-5 is maintained by long-lived type 2 innate lymphoid cells (ILC2) resident in peripheral tissues. ILC2 secrete IL-5 constitutively and are induced to co-express IL-13 during type 2 inflammation, resulting in localized eotaxin production and eosinophil accumulation. In the small intestine where eosinophils and eotaxin are constitutive, 4 ILC2 co-express IL-5 and IL-13, which is enhanced after caloric intake. The circadian synchronizer vasoactive intestinal peptide (VIP) also stimulates ILC2 through the VPAC2 receptor to release IL-5, linking eosinophil levels with metabolic cycling. Tissue ILC2 regulate basal eosinophilopoiesis and tissue eosinophil accumulation through constitutive and stimulated cytokine expression, and this dissociated regulation can be tuned by nutrient intake and central circadian rhythms.
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              Mucins in the mucosal barrier to infection

              S. K. Linden, P. Sutton, N Karlsson … (2008)
              The mucosal tissues of the gastrointestinal, respiratory, reproductive, and urinary tracts, and the surface of the eye present an enormous surface area to the exterior environment. All of these tissues are covered with resident microbial flora, which vary considerably in composition and complexity. Mucosal tissues represent the site of infection or route of access for the majority of viruses, bacteria, yeast, protozoa, and multicellular parasites that cause human disease. Mucin glycoproteins are secreted in large quantities by mucosal epithelia, and cell surface mucins are a prominent feature of the apical glycocalyx of all mucosal epithelia. In this review, we highlight the central role played by mucins in accommodating the resident commensal flora and limiting infectious disease, interplay between underlying innate and adaptive immunity and mucins, and the strategies used by successful mucosal pathogens to subvert or avoid the mucin barrier, with a particular focus on bacteria. Supplementary information The online version of this article (doi:10.1038/mi.2008.5) contains supplementary material, which is available to authorized users.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Immunol Rev
                Journal ID (iso-abbrev): Immunol. Rev
                Journal ID (publisher-id): imr
                Title: Immunological Reviews
                Publisher: BlackWell Publishing Ltd (Oxford, UK )
                ISSN (Print): 0105-2896
                ISSN (Electronic): 1600-065X
                Publication date (Print): July 2014
                Publication date (Electronic): 19 June 2014
                Volume: 260
                Issue: 1
                Pages: 183-205
                Affiliations
                [1 ]Faculty of Life Sciences, University of Manchester Manchester, UK
                Author notes
                Correspondence to: Richard K. Grencis, Faculty of Life Sciences, University of Manchester, A V Hill Building, Oxford Road, Manchester M13 9PT, UK, Tel.: +44 (0) 161 275 5238, Fax: +44 (0) 161 275 3938, e-mail: richard.k.grencis@ 123456manchester.ac.uk
                Article
                DOI: 10.1111/imr.12188
                PMC ID: 4141702
                PubMed ID: 24942690
                SO-VID: e2d05b2e-5dff-4c2c-ba30-56eb3bad0a67
                Copyright © © 2014 The Authors Immunological Reviews Published by John Wiley & Sons Ltd.
                License:

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Subject: Invited Review

                Keywords: parasitic helminth,cytokines,inflammation
                Data availability:
                Keywords: parasitic helminth, cytokines, inflammation

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