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

Besnard, A.-G., Guabiraba Brito, R., Niedbala, W., Palomo, J., Reverchon, F., Shaw, T. N., Couper, K. N., Ryffel, B. and Liew, F. (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. PLoS Pathogens, 11(2), e1004607. (doi: 10.1371/journal.ppat.1004607) (PMID:25659095) (PMCID:PMC4450060)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Liew, Prof Foo and Couper, Dr Kevin and Niedbala, Dr Wanda and Besnard, Dr Anne-Gaelle and Guabiraba Brito, Dr Rodrigo and Shaw, Miss Tovah
Authors: Besnard, A.-G., Guabiraba Brito, R., Niedbala, W., Palomo, J., Reverchon, F., Shaw, T. N., Couper, K. N., Ryffel, B., and Liew, F.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:PLoS Pathogens
Publisher:Public Library of Science
ISSN:1553-7366
ISSN (Online):1553-7374
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in PLoS Pathogens 10(2):e1004607
Publisher Policy:Reproduced under a Creative Commons License
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