Targeting the IL33-NLRP3 axis improves therapy for experimental cerebral malaria

Strangward, P. et al. (2018) Targeting the IL33-NLRP3 axis improves therapy for experimental cerebral malaria. Proceedings of the National Academy of Sciences of the United States of America, 115(28), pp. 7404-7409. (doi: 10.1073/pnas.1801737115) (PMID:29954866) (PMCID:PMC6048513)

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Abstract

Cerebral malaria (CM) is a neurological complication of malaria infection that, despite antimalarial drug treatment, results in fatality or neurodisability in approximately 25% of cases. Thus, there is an urgent clinical need to develop therapies that can improve the efficacy of antimalarial drugs to prevent or reverse cerebral pathology. Here, we show in an experimental mouse model of CM (ECM) that IL33 administration can improve survival and reduce pathology in the brain over antimalarial drugs alone. Mechanistically, we demonstrate that IL33 enhances recovery from ECM by inhibiting NLRP3 inflammasome-induced inflammatory responses within the brain. These results suggest that IL33 and NLRP3 inflammasome inhibitors may be effective adjunctive therapies for CM.

Item Type:Articles
Additional Information:The study was supported by the Medical Research Council (MRC) Grants MR/L008564/1 and MR/R010099/1 and by MRC Career Development Award G0900487 (to K.N.C.). Contributions from S.M.A., M.J.H., and D.B. were supported by MRC Grants MC_PC_16033 and MR/N003586/1.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Liew, Prof Foo
Authors: Strangward, P., Haley, M. J., Albornoz, M. G., Barrington, J., Shaw, T., Dookie, R., Zeef, L., Baker, S. M., Winter, E., Tzeng, T.-C., Golenbock, D. T., Cruickshank, S. M., Allan, S. M., Craig, A., Liew, F. Y., Brough, D., and Couper, K. N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
ISSN:0027-8424
ISSN (Online):1091-6490
Published Online:28 June 2018

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