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      Modulation of haematopoiesis by protozoal and helminth parasites

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          Abstract

          During inflammation, haematopoietic stem cells (HSCs) in the bone marrow (BM) and periphery rapidly expand and preferentially differentiate into myeloid cells that mediate innate immune responses. HSCs can be directed into quiescence or differentiation by sensing alterations to the haematopoietic niche, including cytokines, chemokines, and pathogen‐derived products. Most studies attempting to identify the mechanisms of haematopoiesis have focused on bacterial and viral infections. From intracellular protozoan infections to large multicellular worms, parasites are a global health burden and represent major immunological challenges that remain poorly defined in the context of haematopoiesis. Immune responses to parasites vary drastically, and parasites have developed sophisticated immunomodulatory mechanisms that allow development of chronic infections. Recent advances in imaging, genomic sequencing, and mouse models have shed new light on how parasites induce unique forms of emergency haematopoiesis. In addition, parasites can modify the haematopoiesis in the BM and periphery to improve their survival in the host. Parasites can also induce long‐lasting modifications to HSCs, altering future immune responses to infection, inflammation or transplantation, a term sometimes referred to as central trained immunity. In this review, we highlight the current understanding of parasite‐induced haematopoiesis and how parasites target this process to promote chronic infections.

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          Defining trained immunity and its role in health and disease

          Immune memory is a defining feature of the acquired immune system, but activation of the innate immune system can also result in enhanced responsiveness to subsequent triggers. This process has been termed ‘trained immunity’, a de facto innate immune memory. Research in the past decade has pointed to the broad benefits of trained immunity for host defence but has also suggested potentially detrimental outcomes in immune-mediated and chronic inflammatory diseases. Here we define ‘trained immunity’ as a biological process and discuss the innate stimuli and the epigenetic and metabolic reprogramming events that shape the induction of trained immunity.
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            Trained immunity: A program of innate immune memory in health and disease.

            The general view that only adaptive immunity can build immunological memory has recently been challenged. In organisms lacking adaptive immunity, as well as in mammals, the innate immune system can mount resistance to reinfection, a phenomenon termed "trained immunity" or "innate immune memory." Trained immunity is orchestrated by epigenetic reprogramming, broadly defined as sustained changes in gene expression and cell physiology that do not involve permanent genetic changes such as mutations and recombination, which are essential for adaptive immunity. The discovery of trained immunity may open the door for novel vaccine approaches, new therapeutic strategies for the treatment of immune deficiency states, and modulation of exaggerated inflammation in autoinflammatory diseases.
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              Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis.

              Mononuclear phagocytes, including monocytes, macrophages, and dendritic cells, contribute to tissue integrity as well as to innate and adaptive immune defense. Emerging evidence for labor division indicates that manipulation of these cells could bear therapeutic potential. However, specific ontogenies of individual populations and the overall functional organization of this cellular network are not well defined. Here we report a fate-mapping study of the murine monocyte and macrophage compartment taking advantage of constitutive and conditional CX(3)CR1 promoter-driven Cre recombinase expression. We have demonstrated that major tissue-resident macrophage populations, including liver Kupffer cells and lung alveolar, splenic, and peritoneal macrophages, are established prior to birth and maintain themselves subsequently during adulthood independent of replenishment by blood monocytes. Furthermore, we have established that short-lived Ly6C(+) monocytes constitute obligatory steady-state precursors of blood-resident Ly6C(-) cells and that the abundance of Ly6C(+) blood monocytes dynamically controls the circulation lifespan of their progeny. Copyright © 2013 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                kingston.mills@tcd.ie
                Journal
                Parasite Immunol
                Parasite Immunol
                10.1111/(ISSN)1365-3024
                PIM
                Parasite Immunology
                John Wiley and Sons Inc. (Hoboken )
                0141-9838
                1365-3024
                28 February 2023
                December 2023
                : 45
                : 12 ( doiID: 10.1111/pim.v45.12 )
                : e12975
                Affiliations
                [ 1 ] Wellcome Centre for Integrative Parasitology Institute of Infection and Immunity, University of Glasgow Glasgow UK
                [ 2 ] Immune Regulation Research Group Trinity Biomedical Sciences Institute, Trinity College Dublin Dublin Ireland
                Author notes
                [*] [* ] Correspondence

                Kingston H. G. Mills, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, D02R590, Ireland.

                Email: kingston.mills@ 123456tcd.ie

                Author information
                https://orcid.org/0000-0002-2171-0277
                https://orcid.org/0000-0003-3646-8222
                Article
                PIM12975
                10.1111/pim.12975
                10909493
                36797216
                26f9c39d-d7fd-4526-9e3a-219c25b56640
                © 2023 The Authors. Parasite Immunology published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 07 February 2023
                : 13 December 2022
                : 13 February 2023
                Page count
                Figures: 2, Tables: 1, Pages: 10, Words: 9439
                Funding
                Funded by: Science Foundation Ireland , doi 10.13039/501100001602;
                Award ID: 16/1A/4468
                Funded by: Wellcome Trust , doi 10.13039/100010269;
                Categories
                Invited Review
                Invited Review
                Custom metadata
                2.0
                December 2023
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.3.8 mode:remove_FC converted:03.03.2024

                Immunology
                haematopoiesis,immune modulation,immunological terms,innate immunity,parasite
                Immunology
                haematopoiesis, immune modulation, immunological terms, innate immunity, parasite

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