Journal Article

Behavior of Neutrophil Granulocytes during Toxoplasma gondii Infection in the Central Nervous System

Riek-Burchardt, Monika, Bank, Ute, Düsedau, Henning P., Mueller, Nancy, French, Timothy, Dunay, Ildiko Rita, Biswas, Aindrila, Schüler, Thomas, Dudeck, Anne

2017

Overview

Cerebral toxoplasmosis is characterized by activation of brain resident cells and recruitment of specific immune cell subsets from the periphery to the central nervous system (CNS). Our studies revealed that the rapidly invaded Ly6G neutrophil granulocytes are an early non-lymphoid source of interferon-gamma (IFN-γ), the cytokine known to be the major mediator of host resistance to ( ). Upon selective depletion of Ly6G neutrophils, we detected reduced IFN-γ production and increased parasite burden in the CNS. Ablation of Ly6G cells resulted in diminished recruitment of Ly6C monocytes into the CNS, indicating a pronounced interplay. Additionally, we identified infiltrated Ly6G neutrophils to be a heterogeneous population. The Ly6G CD62-L CXCR4 subset released cathelicidin-related antimicrobial peptide (CRAMP), which can promote monocyte dynamics. On the other hand, the Ly6G CD62-L CXCR4 subset produced IFN-γ to establish early inflammatory response. Collectively, our findings revealed that the recruited Ly6G CXCR4 neutrophil granulocytes display a heterogeneity in the CNS with a repertoire of effector functions crucial in parasite control and immune regulation upon experimental cerebral toxoplasmosis.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Animals / Antibodies / Antimicrobial peptides / Brain / Brain - immunology / Brain - parasitology / Brain - pathology / Cell activation / Central nervous system / Central Nervous System - immunology / Central Nervous System - parasitology / cerebral toxoplasmosis / Cloning / CXCR4 protein / Cysts / Cytokines / Cytokines - metabolism / Disease Models, Animal / Granulocytes / Granulocytes - immunology / Granulocytes - metabolism / Host-parasite interactions / Host-Parasite Interactions - immunology / Immunoregulation / Infections / Inflammation / Inflammation - immunology / Interferon-gamma - metabolism / Leukocytes (granulocytic) / Leukocytes (neutrophilic) / Lymphocytes / Mice / Mice, Inbred C57BL / Microbiology / Microglia - immunology / Microglia - metabolism / Monocytes / Monocytes - immunology / neuroinflammation / neutrophil granulocytes / Neutrophil Infiltration / Neutrophils / Neutrophils - immunology / Neutrophils - metabolism / Parasites / Protozoa / Reactive oxygen species / Reactive Oxygen Species - isolation & purification / Receptors, Chemokine - blood / Toxoplasma - immunology / Toxoplasma gondii / Toxoplasmosis / Toxoplasmosis - immunology / Toxoplasmosis, Cerebral - immunology / Toxoplasmosis, Cerebral - parasitology / Toxoplasmosis, Cerebral - pathology / γ-Interferon