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Malaria in mice brains, and associated inflammation, prevented by Vitamin D intervention – July 2014

Vitamin D Inhibits the Occurrence of Experimental Cerebral Malaria in Mice by Suppressing the Host Inflammatory Response

Xiyue He*, Juan Yan*, Xiaotong Zhu*,†, Qinghui Wang*,‡, Wei Pang*, Zanmei Qi*, Meilian Wang§, Enjie Luo§, Daniel M. Parker†, Margherita T. Cantorna¶, Liwang Cui† and Yaming Cao*
*Department of Immunology, China Medical University, Shenyang 110001, China;
‡Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, China;
§Department of Microbiology and Parasitology, China Medical University, Shenyang 110001, China;
†Department of Entomology, Pennsylvania State University, University Park, PA 16802; and
¶Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, PA 16802
Address correspondence and reprint requests to Dr. Liwang Cui or Dr. Yaming Cao, Department of Entomology, Pennsylvania State University, University Park, PA 16802 (L.C.) or Department of Immunology, China Medical University, Shenyang 110001, China (Y.C.). E-mail addresses: luc2 at psu.edu (L.C.) or ymcao at mail.cmu.edu.cn (Y.C.)

In animal models of experimental cerebral malaria (ECM), neuropathology is associated with an overwhelming inflammatory response and sequestration of leukocytes and parasite-infected RBCs in the brain. In this study, we explored the effect of vitamin D (VD; cholecalciferol) treatment on host immunity and outcome of ECM in C57BL/6 mice during Plasmodium berghei ANKA (PbA) infection. We observed that oral administration of VD both before and after PbA infection completely protected mice from ECM. VD administration significantly dampened the inducible systemic inflammatory responses with reduced circulating cytokines IFN-γ and TNF and decreased expression of these cytokines by the spleen cells. Meanwhile, VD also resulted in decreased expression of the chemokines CXCL9 and CXCL10 and cytoadhesion molecules (ICAM-1, VCAM-1, and CD36) in the brain, leading to reduced accumulation of pathogenic T cells in the brain and ultimately substantial improvement of the blood–brain barriers of PbA-infected mice. In addition, VD inhibited the differentiation, activation, and maturation of splenic dendritic cells. Meanwhile, regulatory T cells and IL-10 expression levels were upregulated upon VD treatment. These data collectively demonstrated the suppressive function of VD on host inflammatory responses, which provides significant survival benefits in the murine ECM model.

This work was supported by National Institutes of Health Grants R01AI099611 and U19AI089672 and Grant-in-Aid LJQ2011084 from the Liaoning Provincial Development Program for Outstanding Young Scholars (China).
The online version of this article contains supplemental material.

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Comment: this is the first indication that vitamin D might deal with an aspect of human malaria - which kills 1 million people each year

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4162 Related to CM.jpg admin 22 Jul, 2014 00:38 68.44 Kb 710
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