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      How Mouse Macrophages Sense What Is Going On

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          Abstract

          Macrophages are central to both innate and adaptive immunity. With few exceptions, macrophages are the first cells that sense trouble and respond to disturbances in almost all tissues and organs. They sense their environment, inhibit or kill pathogens, take up apoptotic and necrotic cells, heal tissue damage, and present antigens to T cells. Although the origins (yolk sac versus monocyte-derived) and phenotypes (functions, gene expression profiles, surface markers) of macrophages vary between tissues, they have many receptors in common that are specific to one or a few molecular species. Here, we review the expression and function of almost 200 key macrophage receptors that help the macrophages sense what is going on, including pathogen-derived molecules, the state of the surrounding tissue cells, apoptotic and necrotic cell death, antibodies and immune complexes, altered self molecules, extracellular matrix components, and cytokines, including chemokines.

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          Most cited references94

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          Cluster analysis and display of genome-wide expression patterns.

          A system of cluster analysis for genome-wide expression data from DNA microarray hybridization is described that uses standard statistical algorithms to arrange genes according to similarity in pattern of gene expression. The output is displayed graphically, conveying the clustering and the underlying expression data simultaneously in a form intuitive for biologists. We have found in the budding yeast Saccharomyces cerevisiae that clustering gene expression data groups together efficiently genes of known similar function, and we find a similar tendency in human data. Thus patterns seen in genome-wide expression experiments can be interpreted as indications of the status of cellular processes. Also, coexpression of genes of known function with poorly characterized or novel genes may provide a simple means of gaining leads to the functions of many genes for which information is not available currently.
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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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              Dopamine controls systemic inflammation through inhibition of NLRP3 inflammasome.

              Inflammasomes are involved in diverse inflammatory diseases, so the activation of inflammasomes needs to be tightly controlled to prevent excessive inflammation. However, the endogenous regulatory mechanisms of inflammasome activation are still unclear. Here, we report that the neurotransmitter dopamine (DA) inhibits NLRP3 inflammasome activation via dopamine D1 receptor (DRD1). DRD1 signaling negatively regulates NLRP3 inflammasome via a second messenger cyclic adenosine monophosphate (cAMP), which binds to NLRP3 and promotes its ubiquitination and degradation via the E3 ubiquitin ligase MARCH7. Importantly, in vivo data show that DA and DRD1 signaling prevent NLRP3 inflammasome-dependent inflammation, including neurotoxin-induced neuroinflammation, LPS-induced systemic inflammation, and monosodium urate crystal (MSU)-induced peritoneal inflammation. Taken together, our results reveal an endogenous mechanism of inflammasome regulation and suggest DRD1 as a potential target for the treatment of NLRP3 inflammasome-driven diseases.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                02 June 2016
                2016
                : 7
                : 204
                Affiliations
                [1] 1Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology , La Jolla, CA, USA
                [2] 2Department of Bioengineering, University of California San Diego , La Jolla, CA, USA
                [3] 3Division of Immune Regulation, La Jolla Institute for Allergy and Immunology , La Jolla, CA, USA
                [4] 4Department of Microbiology, Immunology, and Cancer Biology, University of Virginia , Charlottesville, VA, USA
                [5] 5Department of Genetics, The Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill , Chapel Hill, NC, USA
                Author notes

                Edited by: Janos G. Filep, University of Montreal, Canada

                Reviewed by: Amiram Ariel, University of Haifa, Israel; Joan Clària, Hospital Clinic-Barcelona University School of Medicine, Spain; Ian Dransfield, University of Edinburgh, UK; Marco A. Cassatella, University of Verona, Italy

                *Correspondence: Klaus Ley, klaus@ 123456lji.org

                Specialty section: This article was submitted to Molecular Innate Immunity, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2016.00204
                4890338
                27313577
                6aabcb25-35bd-4253-8784-50ba83322043
                Copyright © 2016 Ley, Pramod, Croft, Ravichandran and Ting.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 16 March 2016
                : 10 May 2016
                Page count
                Figures: 1, Tables: 11, Equations: 0, References: 136, Pages: 17, Words: 12374
                Funding
                Funded by: Office of Extramural Research, National Institutes of Health 10.13039/100006955
                Award ID: R01HL115232, P01 DK091222
                Categories
                Immunology
                Review

                Immunology
                macrophages,pathogens,immunity,defense,inflammation
                Immunology
                macrophages, pathogens, immunity, defense, inflammation

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