期刊
JOURNAL OF INFECTIOUS DISEASES
卷 214, 期 10, 页码 1547-1556出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiw428
关键词
malaria; Tim-3; cell-mediated immunity; lymphocyte exhaustion; Plasmodium falciparum; Plasmodium berghei ANKA
资金
- National Natural Science Foundation of China [81301457, 81130033, 81420108023]
- PUMC Youth Fund
- Fundamental Research Funds for the Central Universities [3332015069]
- Beijing Municipal Science and Technology Commission [Z20130309020037]
Cell-mediated immune responses play important roles in immune protection against Plasmodium infection. However, impaired immunity, such as lymphocyte exhaustion, is a common phenomenon in malaria. T-cell immunoglobulin-and mucin-domain-containing molecule 3 (Tim-3) is an important regulatory molecule in cell-mediated immunity and has been implicated in malaria. In this study, it was found that Tim-3 expression on key populations of lymphocytes was significantly increased in both Plasmodium falciparum-infected patients and Plasmodium berghei ANKA (PbANKA)-infected C57BL/6 mice. Upregulation of Tim-3 led to lymphocyte exhaustion, while blocking Tim-3 signaling with an anti-Tim-3 antibody restored lymphocyte activity in Plasmodium infections. Further, anti-Tim-3 treatment accelerated the parasite clearance and relieved the symptoms of cerebral malaria in PbAN-KA-infected mice. In conclusion, Tim-3 on immune cells negatively regulates cell-mediated immunity against Plasmodium infection, and blocking Tim-3 signaling enhances sterile immunity and may play a protective role during malarial parasite infections.
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