title: Specific depletion of Ly6C(hi) inflammatory monocytes prevents immunopathology in experimental cerebral malaria.
abstract: Plasmodium berghei ANKA (PbA) infection of C57BL/6 mice leads to experimental cerebral malaria (ECM) that is commonly associated with serious T cell mediated damage. In other parasitic infection models, inflammatory monocytes have been shown to regulate Th1 responses but their role in ECM remains poorly defined, whereas neutrophils are reported to contribute to ECM immune pathology. Making use of the recent development of specific monoclonal antibodies (mAb), we depleted in vivo Ly6C(hi) inflammatory monocytes (by anti-CCR2), Ly6G+ neutrophils (by anti-Ly6G) or both cell types (by anti-Gr1) during infection with Ovalbumin-transgenic PbA parasites (PbTg). Notably, the application of anti-Gr1 or anti-CCR2 but not anti-Ly6G antibodies into PbTg-infected mice prevented ECM development. In addition, depletion of Ly6C(hi) inflammatory monocytes but not neutrophils led to decreased IFNγ levels and IFNγ+CD8+ T effector cells in the brain. Importantly, anti-CCR2 mAb injection did not prevent the generation of PbTg-specific T cell responses in the periphery, whereas anti-Gr1 mAb injection strongly diminished T cell frequencies and CTL responses. In conclusion, the specific depletion of Ly6C(hi) inflammatory monocytes attenuated brain inflammation and immune cell recruitment to the CNS, which prevented ECM following Plasmodium infection, pointing out a substantial role of Ly6C+ monocytes in ECM inflammatory processes.
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology, University of Bonn, Bonn, Germany.
authors.forename: Beatrix
authors.initials: B
authors.lastname: Schumak
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology, University of Bonn, Bonn, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Klocke
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology, University of Bonn, Bonn, Germany.
authors.forename: Janina M
authors.initials: JM
authors.lastname: Kuepper
authors.affiliation: Institute of Medical Microbiology, University of Magdeburg, Magdeburg, Germany.
authors.forename: Aindrila
authors.initials: A
authors.lastname: Biswas
authors.affiliation: Department of Neurosurgery, University of Freiburg, Freiburg, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Djie-Maletz
authors.affiliation: Institutes of Molecular Medicine and Experimental Immunology, University of Bonn, Bonn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Limmer
authors.affiliation: VUMC Department of Molecular Cell Biology, Faculty of Medicine Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.affiliation: Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mack
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology, University of Bonn, Bonn, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Hoerauf
authors.affiliation: Institute of Medical Microbiology, University of Magdeburg, Magdeburg, Germany.
authors.forename: Ildiko Rita
authors.initials: IR
authors.lastname: Dunay
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D016779:Malaria, Cerebral / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology* / Q000473:pathology; D010962:Plasmodium berghei