Journal Article

CD8+ T Cells and IFN-γ Mediate the Time-Dependent Accumulation of Infected Red Blood Cells in Deep Organs during Experimental Cerebral Malaria

Teo, Pearline, Ginhoux, Florent, See, Peter Chi Ee, Rénia, Laurent, Chang, Zi Wei, Howland, Shanshan Wu, Malleret, Benoît, Gun, Sin Yee, Wong, Alicia Yoke Wei, Claser, Carla

2011

Overview

Infection with Plasmodium berghei ANKA (PbA) in susceptible mice induces a syndrome called experimental cerebral malaria (ECM) with severe pathologies occurring in various mouse organs. Immune mediators such as T cells or cytokines have been implicated in the pathogenesis of ECM. Red blood cells infected with PbA parasites have been shown to accumulate in the brain and other tissues during infection. This accumulation is thought to be involved in PbA-induced pathologies, which mechanisms are poorly understood. Using transgenic PbA parasites expressing the luciferase protein, we have assessed by real-time in vivo imaging the dynamic and temporal contribution of different immune factors in infected red blood cell (IRBC) accumulation and distribution in different organs during PbA infection. Using deficient mice or depleting antibodies, we observed that CD8(+) T cells and IFN-γ drive the rapid increase in total parasite biomass and accumulation of IRBC in the brain and in different organs 6-12 days post-infection, at a time when mice develop ECM. Other cells types like CD4(+) T cells, monocytes or neutrophils or cytokines such as IL-12 and TNF-α did not influence the early increase of total parasite biomass and IRBC accumulation in different organs. CD8(+) T cells and IFN-γ are the major immune mediators controlling the time-dependent accumulation of P. berghei-infected red blood cells in tissues.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Accumulation / Animal tissues / Animals / Antibodies / Apoptosis / Biology / Biomass / Blood / Blood cells / Brain / Brain - immunology / Brain - parasitology / Brain - pathology / Brain research / CD4 antigen / CD8 antigen / CD8-Positive T-Lymphocytes - immunology / Chemokines / Coma / Cytokines / Cytotoxicity / DNA-Binding Proteins - metabolism / Endothelium / Erythrocytes / Erythrocytes - immunology / Erythrocytes - parasitology / Extracellular matrix / Female / Hypotheses / Immunology / Infections / Interferon / Interferon-gamma - metabolism / Interleukin 12 / Leukocytes (neutrophilic) / Lymphocyte Depletion / Lymphocytes / Lymphocytes T / Malaria / Malaria, Cerebral - immunology / Malaria, Cerebral - parasitology / Male / Mice / Mice, Inbred C57BL / Monocytes / Musculoskeletal system / Myeloid Cells - immunology / Neuroimaging / Organ Specificity - immunology / Organs / Parasites / Pathogenesis / Plasmodium berghei / Plasmodium berghei - physiology / Plasmodium falciparum / Rodents / Science / Studies / Time dependence / Time Factors / Tumor necrosis factor-α / Vector-borne diseases / γ-Interferon