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In this study, we show that a subset of myeloid cells, namely Ly6ChighCCR2+ inflammatory monocytes that infiltrate the brain upon chronic T. gondii infection, plays a decisive role in host defense. Depletion of this monocyte subset resulted in elevated parasite load and decreased survival of infected mice, suggesting their crucial role. Notably, Ly6ChighCCR2+ monocytes governed parasite control due to production of proinflammatory mediators, such as IL-1\u03b1, IL-1\u03b2, IL-6, inducible NO synthase, TNF, and reactive oxygen intermediate. Interestingly, Ly6ChighCCR2+ monocytes were also able to produce the regulatory cytokine IL-10, revealing their dual feature. Moreover, we confirmed by adoptive transfer that the recruited monocytes further develop into two distinct subpopulations contributing to parasite control and profound host defense. The differentiated Ly6CintCCR2+F4\/80int subset upregulated MHC I and MHC II molecules, suggesting dendritic cell properties such as interaction with T cells, whereas the Ly6CnegF4\/80high cell subset displayed elevated phagocytic capacity while upregulating triggering receptor expressed on myeloid cells-2. Finally, we have shown that the recruitment of Ly6Chigh monocytes to the CNS is regulated by P-selectin glycoprotein ligand-1. These results indicate the critical importance of recruited Ly6Chigh monocytes upon cerebral toxoplasmosis and reveal the behavior of further differentiated myeloid-derived mononuclear cell subsets in parasite control and immune regulation of the CNS.<\/jats:p>","DOI":"10.4049\/jimmunol.1402037","type":"journal-article","created":{"date-parts":[[2015,2,26]],"date-time":"2015-02-26T08:28:29Z","timestamp":1424939309000},"page":"3223-3235","source":"Crossref","is-referenced-by-count":109,"title":["Ly6Chigh Monocytes Control Cerebral Toxoplasmosis"],"prefix":"10.1093","volume":"194","author":[{"given":"Aindrila","family":"Biswas","sequence":"first","affiliation":[{"name":"Institute of Medical Microbiology, University of Magdeburg , 39120 Magdeburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dunja","family":"Bruder","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, University of Magdeburg , 39120 Magdeburg ,","place":["Germany"]},{"name":"Immune Regulation Group, Helmholtz Centre for Infection Research , 38124 Braunschweig ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne A","family":"Wolf","sequence":"additional","affiliation":[{"name":"Department of Cellular Neuroscience, Max-Delbrueck-Center for Molecular Medicine , 13092 Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Jeron","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, University of Magdeburg , 39120 Magdeburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Mack","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum Regensburg, Innere Medizin II\/Nephrologie-Transplantation , 93042 Regensburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus M","family":"Heimesaat","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Hygiene, Charit\u00e9-University Medicine Berlin , 12203 Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ildiko Rita","family":"Dunay","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, University of Magdeburg , 39120 Magdeburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,4,1]]},"reference":[{"key":"2025030705384834900_r1","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1111\/j.1600-065X.2010.00992.x","article-title":"Immunology of Toxoplasma gondii","volume":"240","author":"Munoz","year":"2011","journal-title":"Immunol. 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