Erythropoietin protects against murine cerebral malaria through actions on host cellular immunity

Xu Wei, Ying Li, Xiaodan Sun, Xiaotong Zhu, Yonghui Feng, Jun Liu, Yongjun Jiang, Hong Shang, Liwang Cui, Yaming Cao

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Abstract

Cerebral malaria (CM) is associated with excessive host proinflammatory responses and endothelial activation. The hematopoietic hormone erythropoietin (EPO) possesses neuroprotective functions in animal models of ischemic-hypoxic, traumatic, and inflammatory injuries. In the Plasmodium berghei ANKA model of experimental CM (ECM), recombinant human EPO (rhEPO) has shown evident protection against ECM. To elucidate the mechanism of EPO in this ECM model, we investigated the effect of rhEPO on host cellular immune responses. We demonstrated that improved survival of mice with ECM after rhEPO treatment was associated with reduced endothelial activation and improved integrity of the blood-brain barrier. Our results revealed that rhEPO downregulated the inflammatory responses by directly inhibiting the levels and functions of splenic dendritic cells. Conversely, rhEPO treatment led to significant expansion of regulatory T cells and increased expression of the receptor cytotoxic T lymphocyte antigen 4 (CTLA-4). The data presented here provide evidence of the direct effect of rhEPO on host cellular immunity during ECM.

Original languageEnglish (US)
Pages (from-to)165-173
Number of pages9
JournalInfection and Immunity
Volume82
Issue number1
DOIs
StatePublished - Jan 1 2014

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All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Wei, X., Li, Y., Sun, X., Zhu, X., Feng, Y., Liu, J., Jiang, Y., Shang, H., Cui, L., & Cao, Y. (2014). Erythropoietin protects against murine cerebral malaria through actions on host cellular immunity. Infection and Immunity, 82(1), 165-173. https://doi.org/10.1128/IAI.00929-13