title: Critical role of IL-33 receptor ST2 in experimental cerebral malaria development.
abstract: Cerebral malaria, a severe complication of Plasmodium falciparum infection, can be modeled in murine Plasmodium berghei ANKA (PbA) infection. PbA-induced experimental cerebral malaria (ECM) is CD8(+) T-cell mediated, and influenced by TH 1/TH 2 balance. Here, we show that IL-33 expression is increased in brain undergoing ECM and we address the role of the IL-33/ST2 pathway in ECM development. ST2-deficient mice were resistant to PbA-induced neuropathology. They survived >20 days with no ECM neurological sign and a preserved cerebral microcirculation, while WT mice succumbed within 10 days with ECM, brain vascular leakage, distinct microvascular pathology obstruction, and hemorrhages. Parasitemia and brain parasite load were similar in ST2-deficient and WT mice. Protection was accompanied by reduced brain sequestration of activated CD4(+) T cells and perforin(+) CD8(+) T cells. While IFN-γ and T-cell-attracting chemokines CXCL9 and CXCL10 were not affected in the absence of functional ST2 pathway, the local expression of ICAM-1, CXCR3, and LT-α, crucial for ECM development, was strongly reduced, and this may explain the diminished pathogenic T-cell recruitment and resistance to ECM. Therefore, IL-33 is induced in PbA sporozoite infection, and the pathogenic T-cell responses with local microvascular pathology are dependent on IL-33/ST2 signaling, identifying IL-33 as a new actor in ECM development.
authors: CNRS, UMR7355, Orleans, France.|Experimental and Molecular Immunology and Neurogenetics, University of Orleans, Orleans, France.
authors: Jennifer
authors: J
authors: Palomo
authors: CNRS, UMR7355, Orleans, France.|Experimental and Molecular Immunology and Neurogenetics, University of Orleans, Orleans, France.
authors: Flora
authors: F
authors: Reverchon
authors: CNRS, UMR7355, Orleans, France.|Experimental and Molecular Immunology and Neurogenetics, University of Orleans, Orleans, France.
authors: Julie
authors: J
authors: Piotet
authors: CNRS, UMR7355, Orleans, France.|Experimental and Molecular Immunology and Neurogenetics, University of Orleans, Orleans, France.
authors: Anne-Gaelle
authors: AG
authors: Besnard
authors: CNRS, UMR7355, Orleans, France.|Experimental and Molecular Immunology and Neurogenetics, University of Orleans, Orleans, France.
authors: Aurélie
authors: A
authors: Couturier-Maillard
authors: CNRS, UMR7355, Orleans, France.|Experimental and Molecular Immunology and Neurogenetics, University of Orleans, Orleans, France.
authors: Isabelle
authors: I
authors: Maillet
authors: CIMI-Paris (UPMC UMRS CR7, Inserm U1135, CNRS ERL 8255), Paris, France.
authors: Maurel
authors: M
authors: Tefit
authors: CNRS, UMR7355, Orleans, France.|Experimental and Molecular Immunology and Neurogenetics, University of Orleans, Orleans, France.
authors: François
authors: F
authors: Erard
authors: CIMI-Paris (UPMC UMRS CR7, Inserm U1135, CNRS ERL 8255), Paris, France.|Groupe Hospitalier Pitié-Salpêtrière Service Parasitologie-Mycologie, Paris, France.
authors: Dominique
authors: D
authors: Mazier
authors: CNRS, UMR7355, Orleans, France.|Experimental and Molecular Immunology and Neurogenetics, University of Orleans, Orleans, France.
authors: Bernhard
authors: B
authors: Ryffel
authors: CNRS, UMR7355, Orleans, France.|Experimental and Molecular Immunology and Neurogenetics, University of Orleans, Orleans, France.
authors: Valérie F J
authors: VF
authors: Quesniaux
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000473:pathology; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism; D008213:Lymphocyte Activation; D016779:Malaria, Cerebral / Q000209:etiology* / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010962:Plasmodium berghei / Q000276:immunology / Q000472:pathogenicity; D018123:Receptors, Interleukin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D018123:Receptors, Interleukin
keywords: Experimental cerebral malaria; IL-33; Plasmodium berghei ANKA; ST2; Sporozoite