title: T-Cell Immunoglobulin- and Mucin-Domain-Containing Molecule 3 Signaling Blockade Improves Cell-Mediated Immunity Against Malaria.
abstract: 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 PbANKA-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.
authors.affiliation: Ministry of Health Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College.
authors.forename: Nan
authors.initials: N
authors.lastname: Hou
authors.affiliation: Beijing Tropical Medicine Research Institute, Beijing Key Laboratory for Research on Prevention and Treatment of Tropical Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Ministry of Health Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College.
authors.forename: Xianyu
authors.initials: X
authors.lastname: Piao
authors.affiliation: Ministry of Health Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College.
authors.forename: Shuai
authors.initials: S
authors.lastname: Liu
authors.affiliation: Beijing Tropical Medicine Research Institute, Beijing Key Laboratory for Research on Prevention and Treatment of Tropical Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Ministry of Health Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.affiliation: Ministry of Health Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College.|Key Laboratory of Zoonosis, Shenyang Agriculture University, Shenyang City, People's Republic of China.
authors.forename: Qijun
authors.initials: Q
authors.lastname: Chen
mesh_terms: D000818:Animals; D064368:Healthy Volunteers; D000072597:Hepatitis A Virus Cellular Receptor 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D007111:Immunity, Cellular; D008288:Malaria / Q000276:immunology*; D008297:Male; D008810:Mice, Inbred C57BL; D010962:Plasmodium berghei / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*
chemical_list: C448908:HAVCR2 protein, human; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2
keywords: Plasmodium berghei ANKA; Plasmodium falciparum; Tim-3; cell-mediated immunity; lymphocyte exhaustion; malaria