Intestinal Mononuclear Phagocytes in Health and Disease
- Authors: Theodore J. Sanders1, Ulf Yrlid2, Kevin J. Maloy3
- Editor: Siamon Gordon4
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VIEW AFFILIATIONS HIDE AFFILIATIONSAffiliations: 1: Sir William Dunn School of Pathology, Oxford, OX1 3RE, United Kingdom; 2: Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, S-405 30 Gothenburg, Sweden; 3: Sir William Dunn School of Pathology, Oxford, OX1 3RE, United Kingdom; 4: Oxford University, Oxford, United Kingdom
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Received 09 August 2016 Accepted 30 November 2016 Published 20 January 2017
- Correspondence: Kevin J. Maloy, [email protected]

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Abstract:
The intestine is the tissue of the body with the highest constitutive exposure to foreign antigen and is also a common entry portal for many local and systemic pathogens. Therefore, the local immune system has the unenviable task of balancing efficient responses to dangerous pathogens with tolerance toward beneficial microbiota and food antigens. As in most tissues, the decision between tolerance and immunity is critically governed by the activity of local myeloid cells. However, the unique challenges posed by the intestinal environment have necessitated the development of several specialized mononuclear phagocyte populations with distinct phenotypic and functional characteristics that have vital roles in maintaining barrier function and immune homeostasis in the intestine. Intestinal mononuclear phagocyte populations, comprising dendritic cells and macrophages, are crucial for raising appropriate active immune responses against ingested pathogens. Recent technical advances, including microsurgical approaches allowing collection of cells migrating in intestinal lymph, intravital microscopy, and novel gene-targeting approaches, have led to clearer distinctions between mononuclear phagocyte populations in intestinal tissue. In this review, we present an overview of the various subpopulations of intestinal mononuclear phagocytes and discuss their phenotypic and functional characteristics. We also outline their roles in host protection from infection and their regulatory functions in maintaining immune tolerance toward beneficial intestinal antigens.
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Citation: Sanders T, Yrlid U, Maloy K. 2017. Intestinal Mononuclear Phagocytes in Health and Disease. Microbiol Spectrum 5(1):MCHD-0047-2016. doi:10.1128/microbiolspec.MCHD-0047-2016.




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Abstract:
The intestine is the tissue of the body with the highest constitutive exposure to foreign antigen and is also a common entry portal for many local and systemic pathogens. Therefore, the local immune system has the unenviable task of balancing efficient responses to dangerous pathogens with tolerance toward beneficial microbiota and food antigens. As in most tissues, the decision between tolerance and immunity is critically governed by the activity of local myeloid cells. However, the unique challenges posed by the intestinal environment have necessitated the development of several specialized mononuclear phagocyte populations with distinct phenotypic and functional characteristics that have vital roles in maintaining barrier function and immune homeostasis in the intestine. Intestinal mononuclear phagocyte populations, comprising dendritic cells and macrophages, are crucial for raising appropriate active immune responses against ingested pathogens. Recent technical advances, including microsurgical approaches allowing collection of cells migrating in intestinal lymph, intravital microscopy, and novel gene-targeting approaches, have led to clearer distinctions between mononuclear phagocyte populations in intestinal tissue. In this review, we present an overview of the various subpopulations of intestinal mononuclear phagocytes and discuss their phenotypic and functional characteristics. We also outline their roles in host protection from infection and their regulatory functions in maintaining immune tolerance toward beneficial intestinal antigens.

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FIGURE 1
Major subsets of murine mononuclear phagocytes. In the steady-state intestine, resident Mɸ and migratory DCs act synergistically to maintain homeostasis and prevent inflammation. In response to infectious or inflammatory insults, recruited Ly6C+ monocytes and migratory DCs exhibit a proinflammatory phenotype that coordinates protective innate and adaptive immune responses. However, sustained activation of mononuclear phagocytes can drive chronic intestinal inflammation, leading to tissue damage and impaired function. CTL, cytotoxic T lymphocyte; NO, nitric oxide.
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