title: IL-33-mediated protection against experimental cerebral malaria is linked to induction of type 2 innate lymphoid cells, M2 macrophages and regulatory T cells.
abstract: Cerebral malaria (CM) is a complex parasitic disease caused by Plasmodium sp. Failure to establish an appropriate balance between pro- and anti-inflammatory immune responses is believed to contribute to the development of cerebral pathology. Using the blood-stage PbA (Plasmodium berghei ANKA) model of infection, we show here that administration of the pro-Th2 cytokine, IL-33, prevents the development of experimental cerebral malaria (ECM) in C57BL/6 mice and reduces the production of inflammatory mediators IFN-γ, IL-12 and TNF-α. IL-33 drives the expansion of type-2 innate lymphoid cells (ILC2) that produce Type-2 cytokines (IL-4, IL-5 and IL-13), leading to the polarization of the anti-inflammatory M2 macrophages, which in turn expand Foxp3 regulatory T cells (Tregs). PbA-infected mice adoptively transferred with ILC2 have elevated frequency of M2 and Tregs and are protected from ECM. Importantly, IL-33-treated mice deleted of Tregs (DEREG mice) are no longer able to resist ECM. Our data therefore provide evidence that IL-33 can prevent the development of ECM by orchestrating a protective immune response via ILC2, M2 macrophages and Tregs.
authors: Institute of Infection, Immunity and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, United Kingdom.
authors: Anne-Gaelle
authors: AG
authors: Besnard
authors: Institute of Infection, Immunity and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, United Kingdom; INRA, UMR1282, Infectiologie et Santé publique, Nouzilly, France.
authors: Rodrigo
authors: R
authors: Guabiraba
authors: Institute of Infection, Immunity and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, United Kingdom.
authors: Wanda
authors: W
authors: Niedbala
authors: CNRS-UMR7355, Orleans, France and Experimental and Molecular Immunology and Neurogenetics, University of Orleans, Orleans, France.
authors: Jennifer
authors: J
authors: Palomo
authors: CNRS-UMR7355, Orleans, France and Experimental and Molecular Immunology and Neurogenetics, University of Orleans, Orleans, France.
authors: Flora
authors: F
authors: Reverchon
authors: Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors: Tovah N
authors: TN
authors: Shaw
authors: Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors: Kevin N
authors: KN
authors: Couper
authors: CNRS-UMR7355, Orleans, France and Experimental and Molecular Immunology and Neurogenetics, University of Orleans, Orleans, France; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondeboasch, Republic of South Africa.
authors: Bernhard
authors: B
authors: Ryffel
authors: Institute of Infection, Immunity and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, United Kingdom; School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China.
authors: Foo Y
authors: FY
authors: Liew
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018920:Coculture Techniques; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007113:Immunity, Innate; D000067596:Interleukin-33 / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D016779:Malaria, Cerebral / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010962:Plasmodium berghei / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: C506535:Il33 protein, mouse; D000067596:Interleukin-33