Back to Search
Start Over
IL-33-mediated protection against experimental cerebral malaria is linked to induction of type 2 innate lymphoid cells, M2 macrophages and regulatory T cells.
- Source :
-
PLoS pathogens [PLoS Pathog] 2015 Feb 06; Vol. 11 (2), pp. e1004607. Date of Electronic Publication: 2015 Feb 06 (Print Publication: 2015). - Publication Year :
- 2015
-
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.
- Subjects :
- Adoptive Transfer
Animals
Coculture Techniques
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Immunity, Innate
Mice
Mice, Inbred C57BL
Plasmodium berghei immunology
Real-Time Polymerase Chain Reaction
Interleukin-33 immunology
Macrophages immunology
Malaria, Cerebral immunology
T-Lymphocytes, Regulatory immunology
Th2 Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7374
- Volume :
- 11
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- PLoS pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 25659095
- Full Text :
- https://doi.org/10.1371/journal.ppat.1004607