title: Host Resistance to Plasmodium-Induced Acute Immune Pathology Is Regulated by Interleukin-10 Receptor Signaling.
abstract: The resolution of malaria infection is dependent on a balance between proinflammatory and regulatory immune responses. While early effector T cell responses are required for limiting parasitemia, these responses need to be switched off by regulatory mechanisms in a timely manner to avoid immune-mediated tissue damage. Interleukin-10 receptor (IL-10R) signaling is considered to be a vital component of regulatory responses, although its role in host resistance to severe immune pathology during acute malaria infections is not fully understood. In this study, we have determined the contribution of IL-10R signaling to the regulation of immune responses duringPlasmodium bergheiANKA-induced experimental cerebral malaria (ECM). We show that antibody-mediated blockade of the IL-10R duringP. bergheiANKA infection in ECM-resistant BALB/c mice leads to amplified T cell activation, higher serum gamma interferon (IFN-γ) concentrations, enhanced intravascular accumulation of both parasitized red blood cells and CD8+T cells to the brain, and an increased incidence of ECM. Importantly, the pathogenic effects of IL-10R blockade duringP. bergheiANKA infection were reversible by depletion of T cells and neutralization of IFN-γ. Our findings underscore the importance of IL-10R signaling in preventing T-cell- and cytokine-mediated pathology during potentially lethal malaria infections.
authors.affiliation: Laboratory of Pathogen Immunobiology, Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.
authors.forename: Carla
authors.initials: C
authors.lastname: Claser
authors.affiliation: Division of Infection and Immunity, University College London Medical School, London, United Kingdom.|Immunology and Infection Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: J Brian
authors.initials: JB
authors.lastname: De Souza
authors.affiliation: Immunology and Infection Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Thorburn
authors.affiliation: Vascular Immunology Unit, Department of Pathology, School of Medical Sciences, Bosch Institute, The University of Sydney, Camperdown, New South Wales, Australia.
authors.forename: Georges Emile
authors.initials: GE
authors.lastname: Grau
authors.affiliation: Immunology and Infection Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Riley
authors.affiliation: Laboratory of Pathogen Immunobiology, Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.
authors.forename: Laurent
authors.initials: L
authors.lastname: Rénia
authors.affiliation: Immunology and Infection Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom Julius.Hafalla@lshtm.ac.uk.
authors.forename: Julius C R
authors.initials: JCR
authors.lastname: Hafalla
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D057134:Antibodies, Neutralizing / Q000008:administration & dosage; D001921:Brain / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D005260:Female; D007371:Interferon-gamma / Q000097:blood*; D008099:Liver / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D016779:Malaria, Cerebral / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018512:Parasitemia / Q000276:immunology; D010962:Plasmodium berghei / Q000276:immunology*; D053701:Receptors, Interleukin-10 / Q000037:antagonists & inhibitors / Q000276:immunology*; D015398:Signal Transduction
chemical_list: D019138:Antibodies, Blocking; D057134:Antibodies, Neutralizing; D053701:Receptors, Interleukin-10; D007371:Interferon-gamma
keywords: IFN-γ; IL-10; Plasmodium berghei; T cells; immunopathology; malaria