title: Role of IL-10-producing regulatory B cells in control of cerebral malaria in Plasmodium berghei infected mice.
abstract: Cerebral malaria (CM) is a neurological syndrome often occurring in severe malaria. Although CM is known as an immunopathology in brain tissue mediated by excessive proinflammatory cytokines, the immunoregulatory mechanism is poorly understood. Here, we investigated the role of IL-10-producing regulatory B (Breg) cells in modulating CM development in a murine model of Plasmodium berghei ANKA infection. We observed that blood-stage P. berghei induced expansion of IL-10-producing Breg cells in C57BL/6 mice. Adoptive transfer of IL-10(+) Breg cells to P. berghei infected mice significantly reduced the accumulation of NK and CD8(+) T cells and hemorrhage in brain tissue, and improved the survival of the mice compared with control groups, although parasitemia levels were not altered. Treatment of Breg-cell recipient mice with anti-IL-10 receptor mAb blocked the protective effect of Breg cells. Adoptive transfer of CD4(+) CD25(+) Treg cells failed to prevent CM in infected mice. Spleen cells from Breg-cell recipient mice produced increased levels of IL-10 in vitro. Cell co-culture showed that purified IL-10(+) B cells, but not IL-10(-) B cells, promoted IL-10 production by CD4(+) T cells. These results demonstrate that IL-10-producing Breg cells may represent an important mechanism for controlling the immunopathology and prevention of CM associated with P. berghei infection.
authors.affiliation: State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, P.R. China; School of Life Sciences, University of Science and Technology of China, Hefei, P.R. China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Liu
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.forename: Zhaotao
authors.initials: Z
authors.lastname: Li
authors.forename: Yingli
authors.initials: Y
authors.lastname: Han
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Sun
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wang
authors.forename: Boyu
authors.initials: B
authors.lastname: Liu
authors.forename: Zhong
authors.initials: Z
authors.lastname: Su
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology; D016779:Malaria, Cerebral / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010962:Plasmodium berghei / Q000276:immunology*; D053701:Receptors, Interleukin-10 / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation
chemical_list: D000911:Antibodies, Monoclonal; D053701:Receptors, Interleukin-10; D016753:Interleukin-10
keywords: Cerebral malaria; Immunomodulation; Interleukin-10; Plasmodium berghei; Regulatory B cells