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      Monocytes in health and disease — Minireview

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          Monocytes are important cell types of the innate immune system. Recent scientific evidence suggests that monocytes not only play a crucial role in our innate immune system by defending the host from intruding microbial pathogens but they also contribute to the pathogenesis and progression of diseases such as liver fibrosis, atherosclerosis, multiple sclerosis, and tumor metastasis. In addition, monocytes and monocyte-derived macrophages play a crucial beneficial role in the liver fibrosis regression, muscle regeneration, and the clearance of the β-amyloid plaques in Alzheimer’s disease. Here, we summarize the origin, plasticity, and pathogenic potential of monocytes and monocyte-derived macrophages, as well as their positive role in the regression of some common diseases. Elucidating the comprehensive immunological role of monocytes will provide therapeutic advantages in either controlling disease progression or favoring the regression of the disease state.

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          Most cited references 24

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

          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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            TNF/iNOS-producing dendritic cells mediate innate immune defense against bacterial infection.

            Dendritic cells (DCs) present microbial antigens to T cells and provide inflammatory signals that modulate T cell differentiation. While the role of DCs in adaptive immunity is well established, their involvement in innate immune defenses is less well defined. We have identified a TNF/iNOS-producing (Tip)-DC subset in spleens of Listeria monocytogenes-infected mice that is absent from CCR2-deficient mice. The absence of Tip-DCs results in profound TNF and iNOS deficiencies and an inability to clear primary bacterial infection. CD8 and CD4 T cell responses to L. monocytogenes antigens are preserved in CCR2-deficient mice, indicating that Tip-DCs are not essential for T cell priming. Tip-DCs, as the predominant source of TNF and iNOS during L. monocytogenes infection, orchestrate and mediate innate immune defense against this intracellular bacterial pathogen.
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              Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions.

              Microglia are crucially important myeloid cells in the CNS and constitute the first immunological barrier against pathogens and environmental insults. The factors controlling microglia recruitment from the blood remain elusive and the direct circulating microglia precursor has not yet been identified in vivo. Using a panel of bone marrow chimeric and adoptive transfer experiments, we found that circulating Ly-6C(hi)CCR2(+) monocytes were preferentially recruited to the lesioned brain and differentiated into microglia. Notably, microglia engraftment in CNS pathologies, which are not associated with overt blood-brain barrier disruption, required previous conditioning of brain (for example, by direct tissue irradiation). Our results identify Ly-6C(hi)CCR2(+) monocytes as direct precursors of microglia in the adult brain and establish the importance of local factors in the adult CNS for microglia engraftment.

                Author and article information

                European Journal of Microbiology and Immunology
                Akadémiai Kiadó
                1 June 2012
                13 June 2012
                : 2
                : 2 ( otherID: K022535X4502 )
                : 97-102
                [ 1 ] Philipps University-Marburg Department of Dermatology and Allergology Baldingerstrasse D-35033 Marburg Germany
                [ 2 ] University Hospital Aachen Department of Internal Medicine III Aachen Germany
                [ 3 ] Otto-von-Guericke University Institute of Medical Microbiology Magdeburg Germany
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