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The p75<jats:sup>NTR<\/jats:sup> is not exclusively expressed by neurons but also by certain immune cells, implying a role for neurotrophin signaling in the immune system. In this study, we investigated the effect of p75<jats:sup>NTR<\/jats:sup> on innate immune cell behavior and on neuronal morphology upon chronic <jats:italic>Toxoplasma gondii<\/jats:italic> (<jats:italic>T. gondii<\/jats:italic>) infection\u2010induced neuroinflammation. Characterization of the immune cells in the periphery and central nervous system (CNS) revealed that innate immune cell subsets in the brain upregulated p75<jats:sup>NTR<\/jats:sup> upon infection in wild\u2010type mice. Although cell recruitment and phagocytic capacity of p75<jats:sup>NTRexonIV<\/jats:sup> knockout (p75<jats:sup>\u2212\/\u2212<\/jats:sup>) mice were not impaired, the activation status of resident microglia and recruited myeloid cell subsets was altered. Importantly, recruited mononuclear cells in brains of infected p75<jats:sup>\u2212\/\u2212<\/jats:sup> mice upregulated the production of the cytokines interleukin (IL)\u201010, IL\u20106 as well as IL\u20101\u03b1. Protein levels of proBDNF, known to negatively influence neuronal morphology by binding p75<jats:sup>NTR<\/jats:sup>, were highly increased upon chronic infection in the brain of wild\u2010type and p75<jats:sup>\u2212\/\u2212<\/jats:sup> mice. Moreover, upon infection the activated immune cells contributed to the proBDNF release. Notably, the neuroinflammation\u2010induced changes in spine density were rescued in the p75<jats:sup>\u2212\/\u2212<\/jats:sup> mice. In conclusion, these findings indicate that neurotrophin signaling via the p75<jats:sup>NTR<\/jats:sup> affects innate immune cell behavior, thus, influencing the structural plasticity of neurons under inflammatory conditions.<\/jats:p>","DOI":"10.1002\/glia.23553","type":"journal-article","created":{"date-parts":[[2018,12,31]],"date-time":"2018-12-31T22:12:40Z","timestamp":1546294360000},"page":"193-211","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["p75<sup>NTR<\/sup> regulates brain mononuclear cell function and neuronal structure in <i>Toxoplasma<\/i> infection\u2010induced neuroinflammation"],"prefix":"10.1002","volume":"67","author":[{"given":"Henning Peter","family":"D\u00fcsedau","sequence":"first","affiliation":[{"name":"Otto\u2010von\u2010Guericke University Magdeburg, Institute of Inflammation and Neurodegeneration, Medical Faculty  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Kleveman","sequence":"additional","affiliation":[{"name":"Division of Cellular Neurobiology Zoological Institute, TU Braunschweig  Braunschweig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caio Andreeta","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"Otto\u2010von\u2010Guericke University Magdeburg, Institute of Inflammation and Neurodegeneration, Medical Faculty  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aindrila","family":"Biswas","sequence":"additional","affiliation":[{"name":"Otto\u2010von\u2010Guericke University Magdeburg, Institute of Inflammation and Neurodegeneration, Medical Faculty  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Steffen","sequence":"additional","affiliation":[{"name":"Otto\u2010von\u2010Guericke University Magdeburg, Institute of Inflammation and Neurodegeneration, Medical Faculty  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Kliche","sequence":"additional","affiliation":[{"name":"Otto\u2010von\u2010Guericke University, Institute for Molecular and Clinical Immunology, Medical Faculty  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Haak","sequence":"additional","affiliation":[{"name":"Division of Cellular Neurobiology Zoological Institute, TU Braunschweig  Braunschweig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Zagrebelsky","sequence":"additional","affiliation":[{"name":"Division of Cellular Neurobiology Zoological Institute, TU Braunschweig  Braunschweig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Korte","sequence":"additional","affiliation":[{"name":"Division of Cellular Neurobiology Zoological Institute, TU Braunschweig  Braunschweig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9900-8605","authenticated-orcid":false,"given":"Ildiko Rita","family":"Dunay","sequence":"additional","affiliation":[{"name":"Otto\u2010von\u2010Guericke University Magdeburg, Institute of Inflammation and Neurodegeneration, Medical Faculty  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,12,30]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.10135"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.69.6.1019"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2000.1182"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1402037"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00259"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/pim.12173"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/1759091417696161"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.2174\/187152711796235032"},{"issue":"1","key":"e_1_2_6_10_1","first-page":"33","article-title":"Role of TNF and IL\u20101 in infections with toxoplasma gondii","volume":"69","author":"Chang H. 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