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      Galectin-3 in M2 Macrophages Plays a Protective Role in Resolution of Neuropathology in Brain Parasitic Infection by Regulating Neutrophil Turnover

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      The Journal of Neuroscience
      Society for Neuroscience

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          Abstract

          <p class="first" id="d1879269e144">Macrophages/microglia with M2-activation phenotype are thought to play important anti-inflammatory and tissue reparative functions in the brain, yet the molecular bases of their functions in the CNS remain to be clearly defined. In a preclinical model of neurocysticercosis using brain infection with a parasite <i>Mesocestoides corti</i>, we previously reported the presence of large numbers of M2 cells in the CNS. In this study using female mice, we report that M2 macrophages in the parasite-infected brain display abundant galectin-3 expression. Disease severity was increased in <i>Galectin-3</i> <sup>−/−</sup> mice correlating with increased neurological defects, augmented cell death and, importantly, massive accumulation of neutrophils and M2 macrophages in the CNS of these mice. Because neutrophil clearance by efferocytosis is an important function of M2 macrophages, we investigated a possible role of galectin-3 in this process. Indeed, galectin-3-deficient M2 macrophages exhibited a defect in efferocytic clearance of neutrophils <i>in vitro</i>. Furthermore, adoptive transfer of M2 macrophages from galectin-3-sufficient WT mice reduced neutrophilia in the CNS and ameliorated disease severity in parasite-infected <i>Galectin-3</i> <sup>−/−</sup> mice. Together, these results demonstrate, for the first time, a novel role of galectin-3 in M2 macrophage function in neutrophil turnover and resolution of inflammatory pathology in the CNS. This likely will have implications in neurocysticercosis and neuroinflammatory diseases. </p><p id="d1879269e165"> <b>SIGNIFICANCE STATEMENT</b> Macrophages/microglia with M1-activation phenotype are thought to promote CNS pathology, whereas M2-anti-inflammatory phenotype promote CNS repair. However, the mechanisms regulating M2 cell-protective functions in the CNS microenvironment are undefined. The current study reports that helminth infection of the brain induces an increased expression of galectin-3 in M2 macrophages accumulated in the CNS. Using multiple experimental models <i>in vivo</i> and <i>in vitro</i>, they show that galectin-3 in M2 macrophages functions to clear neutrophils accumulated in the CNS. Importantly, galectin-3 in M2 macrophages plays a central role in the containment of neuropathology and disease severity. These results provide a direct mechanistic evidence of the protective function of M2 macrophages in the CNS. </p>

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          Author and article information

          Journal
          The Journal of Neuroscience
          J. Neurosci.
          Society for Neuroscience
          0270-6474
          1529-2401
          July 25 2018
          July 25 2018
          July 25 2018
          June 26 2018
          : 38
          : 30
          : 6737-6750
          Article
          10.1523/JNEUROSCI.3575-17.2018
          6067078
          29946038
          bdc717de-dc4b-4828-9571-6ac89803c856
          © 2018
          History

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