Silva, M. T. When two is better than one: macrophages and neutrophils work in concert in innate immunity as complementary and cooperative partners of a myeloid phagocyte system. J. Leukoc. Biol. 87, 93-106

Instituto de Biologia Molecular e Celular, Rua do Campo Alegre 823, Porto, Portugal.
Journal of leukocyte biology (Impact Factor: 4.29). 01/2010; 87(1):93-106. DOI: 10.1189/jlb.0809549
Source: PubMed


The antimicrobial effector activity of phagocytes is crucial in the host innate defense against infection, and the classic view is that the phagocytes operating against intracellular and extracellular microbial pathogens are,respectively, macrophages and neutrophils. As a result of the common origin of the two phagocytes, they share several functionalities, including avid phagocytosis,similar kinetic behavior under inflammatory/infectious conditions, and antimicrobial and immunomodulatory activities. However, consequent to specialization during their differentiation, macrophages and neutrophils acquire distinctive, complementary features that originate different levels of antimicrobial capacities and cytotoxicity and different tissue localization and lifespan.This review highlights data suggesting the perspective that the combination of overlapping and complementary characteristics of the two professional phagocytes promotes their cooperative participation as effectors and modulators in innate immunity against infection and as orchestrators of adaptive immunity. In the concerted activities operating in antimicrobial innate immunity, macrophages and neutrophils are not able to replace each other. The common and complementary developmental,kinetic, and functional properties of neutrophils and macrophages make them the effector arms of a myeloid phagocyte system that groups neutrophils with members of the old mononuclear phagocyte system. The use by mammals of a system with two dedicated phagocytic cells working cooperatively represents an advantageous innate immune attack strategy that allows the efficient and safe use of powerful but dangerous microbicidal molecules.This crucial strategy is a target of key virulence mechanisms of successful pathogens.

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    • "After karyorrhexis extensive plasma membrane blebbing occurs forming apoptotic bodies which contains organelle and nuclear fragments in their cytoplasm (Elmore, 2007). Cells of myeloid series i.e., macrophages are main cells involved in apoptotic cells phagocytosis and thus can result in passive necrosis (hetrophagic necrosis) of phagocytized apoptotic cells (Silva, 2010; Henson and Hume, 2006; He et al., 2009; Odaka and Mizuochi, 1999; McIlroy et al., 2000). Apoptotic cells does not involve any inflammatory reaction as involved by necrotic cells because their plasma membrane remains intact and apoptotic cells are immediately engulfed by macrophages called as " Tingible body macrophages " so that not getting enough time to release their anti-inflammatory cytokines into the interstitial tissues (Elmore, 2007). "

    Asian Journal of Animal and Veterinary Advances 09/2015; 10(10). DOI:10.3923/ajava.2015.646.668 · 0.87 Impact Factor
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    • "However, a failure of neutrophil apoptosis or phagocytosis by macrophages would shew the immune response to an un-resolving and chronic inflammation (Heasman et al., 2003). It has been reported that neutrophils had a crucial role in the pathogenesis of chronic inflammation disease , such as chronic obstructive pulmonary diseases (Snelgrove et al., 2010), tuberculosis (Silva, 2010) and sepsis (Alves-Filho et al., 2010). Increasing evidence indicates that neuthophils play an important role in regulating the adaptive immune response (Abi Abdallah et al., 2011; Beauvillain et al., 2007; Tillack et al., 2012). "
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    ABSTRACT: During chronic inflammation, prolonged over-reactive immune response may lead to tissue destruction, while immune suppression hinders tissue repair and pathogen elimination. Therefore, precise regulation of the immune response is needed to avoid immuno-pathology. Interferon-gamma (IFN-γ) is widely used in clinical treatment of inflammatory diseases. However, the underlying mechanism remains unclear. Here, we evaluated the role of IFN-γ on CD11b(+)Gr-1(+) myeloid cell differentiation and function, using a heat-killed Mycobacterium bovis BCG-induced chronic inflammation model. After challenge with heat-killed BCG, two subpopulations of CD11b(+)Gr-1(+) myeloid cells were generated in the mouse spleen. Phenotypical, morphological and functional analysis indicated that the CD11b(+)Gr-1(high) Ly6G(high) Ly6C(low) subset was neutrophil-like myeloid-derived inducer cells (N-MDICs), which promoted T cell activation, while the other subset was CD11b(+)Gr-1(low) Ly6G(neg) Ly6C(high) monocyte-like myeloid-derived suppressor cells (M-MDSCs) that displayed extensive suppressor function. IFN-γ treatment dampened N-MDICs-mediated T cell activation through up-regulating T cell suppressive mediators, reactive oxygen species (ROS) and arginase I. While for M-MDSCs, IFN-γ reduced their suppressing activity by decreasing the arginase activity. Our study provides evidence that IFN-γ balances the over-reactive vs compromised immune response through different regulation of distinct myeloid subsets, and therefore displays significant therapeutic potential for effective immuno-therapy of chronic inflammatory diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Molecular Immunology 05/2015; 66(2). DOI:10.1016/j.molimm.2015.05.011 · 2.97 Impact Factor
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    • "Tissue damage and repair involves the complex interactions between different populations of cells and their coordinated cell movement (Nathan, 2006; Silva, 2010; Sindrilaru and Scharffetter-Kochanek, 2013; Abtin et al., 2014). The mechanisms through which these interactions are orchestrated to mediate resolution of inflammation, a key step in tissue repair, remain largely unknown (Nathan and Ding, 2010). "
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    ABSTRACT: Tissue damage induces early recruitment of neutrophils through redox-regulated Src family kinase (SFK) signaling in neutrophils. Redox-SFK signaling in epithelium is also necessary for wound resolution and tissue regeneration. How neutrophil-mediated inflammation resolves remains unclear. In this paper, we studied the interactions between macrophages and neutrophils in response to tissue damage in zebrafish and found that macrophages contact neutrophils and induce resolution via neutrophil reverse migration. We found that redox-SFK signaling through p22phox and Yes-related kinase is necessary for macrophage wound attraction and the subsequent reverse migration of neutrophils. Importantly, macrophage-specific reconstitution of p22phox revealed that macrophage redox signaling is necessary for neutrophil reverse migration. Thus, redox-SFK signaling in adjacent tissues is essential for coordinated leukocyte wound attraction and repulsion through pathways that involve contact-mediated guidance. © 2014 Tauzin et al.
    The Journal of Cell Biology 12/2014; 207(5):589-98. DOI:10.1083/jcb.201408090 · 9.83 Impact Factor
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