1. Vitamin D inhibits the occurrence of experimental cerebral malaria in mice by suppressing the host inflammatory response.
- Author
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He X, Yan J, Zhu X, Wang Q, Pang W, Qi Z, Wang M, Luo E, Parker DM, Cantorna MT, Cui L, and Cao Y
- Subjects
- Administration, Oral, Animals, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Dendritic Cells immunology, Dendritic Cells pathology, Down-Regulation immunology, Female, Growth Inhibitors administration & dosage, Growth Inhibitors therapeutic use, Host-Parasite Interactions immunology, Immunosuppressive Agents therapeutic use, Inflammation immunology, Inflammation pathology, Inflammation prevention & control, Interferon-gamma antagonists & inhibitors, Interferon-gamma biosynthesis, Malaria, Cerebral pathology, Mice, Mice, Inbred C57BL, Primary Cell Culture, Random Allocation, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory pathology, Tumor Necrosis Factor-alpha antagonists & inhibitors, Tumor Necrosis Factor-alpha biosynthesis, Up-Regulation immunology, Vitamin D therapeutic use, Anti-Inflammatory Agents, Non-Steroidal administration & dosage, Immunosuppressive Agents administration & dosage, Malaria, Cerebral immunology, Malaria, Cerebral prevention & control, Plasmodium berghei immunology, Vitamin D administration & dosage
- Abstract
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., (Copyright © 2014 by The American Association of Immunologists, Inc.)
- Published
- 2014
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