Roles of HSV-1 infection-induced microglial immune responses in CNS diseases: friends or foes?

Abstract

Microglia, as brain-resident macrophages, are the first line of defense against brain invading pathogens. Further, their dysfunction has been recognized to be closely associated with mounting CNS diseases. Of note, chronic HSV-1 infection leads to the persistent activation of microglia, which elicit a comprehensive response by generating certain factors with neurotoxic and neuroprotective effects. CNS infection with HSV-1 results in herpes simplex encephalitis and herpes simplex keratitis. Microglial immune response plays a crucial role in the development of these diseases. Moreover, HSV-1 infection is strongly associated with several CNS diseases, especially Alzheimer’s disease and schizophrenia. These CNS diseases can be effectively ameliorated by eliciting an appropriate immune response, such as inhibition of microglial proliferation and activation. Therefore, it is crucial to reassess the positive and negative roles of microglia in HSV-1 CNS infection for a more comprehensive and detailed understanding of the relationship between microglia and CNS diseases. Hence, the present review focuses on the dual roles of microglia in mediating HSV-1 CNS infection, as well as on the strategy of targeting microglia to ameliorate CNS diseases. Further research in this field can help comprehensively elucidate the dual role of the microglial immune response in HSV-1 CNS infection, providing a theoretical basis for identifying therapeutic targets against overactive microglia in CNS diseases and HSV-1 infection.

Keywords:

• HSV-1
• Microglia
• CNS diseases
• inflammation
• innate immunity

Author contributions

Yiliang Wang: conception, design, collection and/or assembly of references, discussion, interpretation, and manuscript writing; Jiaoyan Jia and Yun Wang: collection and/or assembly of references, interpretation, and manuscript writing; Feng Li, Xiaowei Song, Shurong Qin, Zhaoyang Wang: collection and/or assembly of references; Kaio Kitazato, and Yifei Wang: conception, design, interpretation, and final approval of the manuscript.

Disclosure statement

All authors declare that they have no conflicts of interest.

Additional information

Funding

This work was supported by grants from the National Natural Science Foundation of China [nos. 81603341, and 81573471]; the Science and Technology Program of Guangzhou, China [201604020178]; Key Projects of Biological Industry Science & Technology of Guangzhou China [grant no. 201504291048224]; Foundation of key Laboratory of the Ministry of Education [2016RF01]; and Science & Technology Plan Program of Guangdong Province China [grant no. 2015A050502028].