title: Ly6C(high) monocytes control cerebral toxoplasmosis.
abstract: Cerebral infection with the parasite Toxoplasma gondii is followed by activation of resident cells and recruitment of immune cells from the periphery to the CNS. In this study, we show that a subset of myeloid cells, namely Ly6C(high)CCR2(+) 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, Ly6C(high)CCR2(+) monocytes governed parasite control due to production of proinflammatory mediators, such as IL-1α, IL-1β, IL-6, inducible NO synthase, TNF, and reactive oxygen intermediate. Interestingly, Ly6C(high)CCR2(+) 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 Ly6C(int)CCR2(+)F4/80(int) subset upregulated MHC I and MHC II molecules, suggesting dendritic cell properties such as interaction with T cells, whereas the Ly6C(neg)F4/80(high) cell subset displayed elevated phagocytic capacity while upregulating triggering receptor expressed on myeloid cells-2. Finally, we have shown that the recruitment of Ly6C(high) monocytes to the CNS is regulated by P-selectin glycoprotein ligand-1. These results indicate the critical importance of recruited Ly6C(high) 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.
authors.affiliation: Institute of Medical Microbiology, University of Magdeburg, 39120 Magdeburg, Germany;
authors.forename: Aindrila
authors.initials: A
authors.lastname: Biswas
authors.affiliation: Institute of Medical Microbiology, University of Magdeburg, 39120 Magdeburg, Germany; Immune Regulation Group, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany;
authors.forename: Dunja
authors.initials: D
authors.lastname: Bruder
authors.affiliation: Department of Cellular Neuroscience, Max-Delbrueck-Center for Molecular Medicine, 13092 Berlin, Germany;
authors.forename: Susanne A
authors.initials: SA
authors.lastname: Wolf
authors.affiliation: Institute of Medical Microbiology, University of Magdeburg, 39120 Magdeburg, Germany;
authors.forename: Andreas
authors.initials: A
authors.lastname: Jeron
authors.affiliation: Universitätsklinikum Regensburg, Innere Medizin II/Nephrologie-Transplantation, 93042 Regensburg, Germany; and.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mack
authors.affiliation: Department of Microbiology and Hygiene, Charité-University Medicine Berlin, 12203 Berlin, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Heimesaat
authors.affiliation: Institute of Medical Microbiology, University of Magdeburg, 39120 Magdeburg, Germany; ildikodunay@gmail.com.
authors.forename: Ildiko Rita
authors.initials: IR
authors.lastname: Dunay
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D016130:Immunophenotyping; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism*; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010587:Phagocytosis / Q000276:immunology; D010641:Phenotype; D054390:Receptors, CCR2 / Q000378:metabolism; D016781:Toxoplasmosis, Cerebral / Q000276:immunology* / Q000469:parasitology / Q000473:pathology
chemical_list: D000950:Antigens, Ly; D016207:Cytokines; C494192:Ly-6C antigen, mouse; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D054390:Receptors, CCR2