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

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IL-33-mediated protection against experimental cerebral malaria is linked to induction of type 2 innate lymphoid cells, M2 macrophages and regulatory T cells.
Authors:	Besnard, Anne-Gaelle Guabiraba, Rodrigo Niedbala, Wanda Palomo, Jennifer Reverchon, Flora Shaw, Tovah N Couper, Kevin N Ryffel, Bernhard Liew, Foo Y
Citation:	Besnard AG, etal., PLoS Pathog. 2015 Feb 6;11(2):e1004607. doi: 10.1371/journal.ppat.1004607. eCollection 2015 Feb.
RGD ID:	39938955
Pubmed:	PMID:25659095 (View Abstract at PubMed)
PMCID:	PMC4450060 (View Article at PubMed Central)
DOI:	DOI:10.1371/journal.ppat.1004607 (Journal Full-text)
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.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
IL33	Human	cerebral malaria	treatment	ISO	Il33 (Mus musculus)		RGD
Il33	Rat	cerebral malaria	treatment	ISO	Il33 (Mus musculus)		RGD
Il33	Mouse	cerebral malaria	treatment	IDA			RGD

Objects Annotated

Genes (Rattus norvegicus)

Il33 (interleukin 33)

Genes (Mus musculus)

Il33 (interleukin 33)

Genes (Homo sapiens)

IL33 (interleukin 33)

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