Open AccessThe immunomodulatory effect of microglia on ECM neuroinflammation via the PD‐1/PD‐L1 pathway
Author(s) -
Shen Yan,
Li Yinghui,
Zhu Qinghao,
Wang Jun,
Huang Yuxiao,
Liang Jiao,
Wu Xingan,
Zhao Ya
Publication year - 2022
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.13760
Subject(s) - microglia , neuroinflammation , immune system , cerebral malaria , plasmodium berghei , immunology , microbiology and biotechnology , chemistry , medicine , biology , inflammation , plasmodium falciparum , malaria
The experimental cerebral malaria (ECM) model in C57BL/6 mice infected with Plasmodium berghei ANKA (PbA) has revealed microglia are involved in the ECM immune microenvironment. However, the regulation of microglia in the ECM immune response is not clear, and there is no safe and efficient treatment clinically for the protection of the nerve cells. Aims To elucidate the negative regulation mechanism in the ECM brain mediated by microglia. Furthermore, to investigate protective effect of the appropriate enhancement of the PD‐1/PD‐L1 pathway in the brain against ECM through the intrathecal injection of the adenovirus expressing PDL1‐IgG1Fc fusion protein. Results The PD‐1/PD‐L1 pathway was induced in the ECM brain and showed an upregulation in the microglia. Deep single‐cell analysis of immune niches in the ECM brainstem indicated that the microglia showed obvious heterogeneity and activation characteristics. Intrathecal injection of recombinant adenovirus expressing PD‐L1 repressed the neuroinflammation and alleviated ECM symptoms. In addition, the synergistic effect of artemisinin and intracranial immunosuppression mediated by PD‐L1 was more efficacious than either treatment alone. Conclusion The appropriate enhancement of the PD‐1/PD‐L1 pathway in the early stage of ECM has an obvious protective effect on the maintenance of immune microenvironment homeostasis in the brain. Regulating microglia and the PD‐1/PD‐L1 pathway could be considered as a promising approach for protection against human cerebral malaria in the future.