title: Vitamin D inhibits the occurrence of experimental cerebral malaria in mice by suppressing the host inflammatory response.
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.
authors: Department of Immunology, China Medical University, Shenyang 110001, China;
authors: Xiyue
authors: X
authors: He
authors: Department of Immunology, China Medical University, Shenyang 110001, China;
authors: Juan
authors: J
authors: Yan
authors: Department of Immunology, China Medical University, Shenyang 110001, China; Department of Entomology, Pennsylvania State University, University Park, PA 16802; and.
authors: Xiaotong
authors: X
authors: Zhu
authors: Department of Immunology, China Medical University, Shenyang 110001, China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, China;
authors: Qinghui
authors: Q
authors: Wang
authors: Department of Immunology, China Medical University, Shenyang 110001, China;
authors: Wei
authors: W
authors: Pang
authors: Department of Immunology, China Medical University, Shenyang 110001, China;
authors: Zanmei
authors: Z
authors: Qi
authors: Department of Microbiology and Parasitology, China Medical University, Shenyang 110001, China;
authors: Meilian
authors: M
authors: Wang
authors: Department of Microbiology and Parasitology, China Medical University, Shenyang 110001, China;
authors: Enjie
authors: E
authors: Luo
authors: Department of Entomology, Pennsylvania State University, University Park, PA 16802; and.
authors: Daniel M
authors: DM
authors: Parker
authors: Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, PA 16802.
authors: Margherita T
authors: MT
authors: Cantorna
authors: Department of Entomology, Pennsylvania State University, University Park, PA 16802; and luc2@psu.edu ymcao@mail.cmu.edu.cn.
authors: Liwang
authors: L
authors: Cui
authors: Department of Immunology, China Medical University, Shenyang 110001, China; luc2@psu.edu ymcao@mail.cmu.edu.cn.
authors: Yaming
authors: Y
authors: Cao
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000627:therapeutic use; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D006790:Host-Parasite Interactions / Q000276:immunology; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016779:Malaria, Cerebral / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D010962:Plasmodium berghei / Q000276:immunology*; D061251:Primary Cell Culture; D011897:Random Allocation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015854:Up-Regulation / Q000276:immunology; D014807:Vitamin D / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D006131:Growth Inhibitors; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D014807:Vitamin D; D007371:Interferon-gamma