Journal Article

Specific depletion of Ly6C(hi) inflammatory monocytes prevents immunopathology in experimental cerebral malaria

Klocke, Katrin, Schumak, Beatrix, Dunay, Ildiko Rita, Kuepper, Janina M, Biswas, Aindrila, Hoerauf, Achim, Mack, Matthias, Djie-Maletz, Andrea, van Rooijen, Nico, Limmer, Andreas

2015

Overview

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.

• Publisher: Public Library of Science (PLoS)
• Subject: Animals / Brain - immunology / Brain - pathology / Disease Models, Animal / Malaria, Cerebral - immunology / Malaria, Cerebral - pathology / Mice / Mice, Inbred C57BL / Monocytes - immunology / Monocytes - pathology / Plasmodium berghei