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PLoS Pathog. 2015 Feb 6;11(2):e1004607. doi: 10.1371/journal.ppat.1004607. eCollection 2015.

IL-33-mediated protection against experimental cerebral malaria is linked to induction of type 2 innate lymphoid cells, M2 macrophages and regulatory T cells.

Author information

  • 1Institute of Infection, Immunity and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, United Kingdom.
  • 2Institute of Infection, Immunity and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, United Kingdom; INRA, UMR1282, Infectiologie et Santé publique, Nouzilly, France.
  • 3CNRS-UMR7355, Orleans, France and Experimental and Molecular Immunology and Neurogenetics, University of Orleans, Orleans, France.
  • 4Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
  • 5CNRS-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.
  • 6Institute 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.

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.

PMID:
25659095
[PubMed - indexed for MEDLINE]
PMCID:
PMC4450060
Free PMC Article
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