Microglia Reduce Herpes Simplex Virus 1 Lethality of Mice with Decreased T Cell and Interferon Responses in Brains

• Published in: International journal of molecular sciences Vol. 22; no. 22; p. 12457
• Main Authors: Tsai, Meng-Shan, Wang, Li-Chiu, Tsai, Hsien-Yang, Lin, Yu-Jheng, Wu, Hua-Lin, Tzeng, Shun-Fen, Hsu, Sheng-Min, Chen, Shun-Hua
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 18.11.2021; MDPI
• Subjects: Animals; Antigens; Brain; Brain - pathology; Brain - virology; CD4 antigen; CD4-Positive T-Lymphocytes - pathology; CD4-Positive T-Lymphocytes - virology; CD8 antigen; CD8-Positive T-Lymphocytes - pathology; CD8-Positive T-Lymphocytes - virology; Cell activation; Cell Count; Cornea - pathology; Cornea - virology; Cytokines; Depletion; Disease Models, Animal; Encephalitis; Female; Flow cytometry; Gene Expression Regulation; Herpes simplex; Herpes Simplex - metabolism; Herpes Simplex - mortality; Herpes Simplex - pathology; Herpes Simplex - virology; herpes simplex virus 1; Herpes viruses; Herpesvirus 1, Human - growth & development; Herpesvirus 1, Human - pathogenicity; Humans; Infections; Infectivity; Interferon; Interferon-beta - genetics; Interferon-beta - metabolism; Interferon-gamma - genetics; Interferon-gamma - metabolism; Leukocytes (neutrophilic); Lymphocytes; Lymphocytes T; Macrophages; Macrophages - pathology; Macrophages - virology; Mice; Mice, Inbred C57BL; Microglia; Microglia - drug effects; Microglia - pathology; Microglia - virology; Mortality; Neurons; Neurons - pathology; Neurons - virology; Neutrophils; Neutrophils - pathology; Neutrophils - virology; Organic Chemicals - toxicity; Pathogenesis; Rodents; Signal Transduction; STAT1 Transcription Factor - genetics; STAT1 Transcription Factor - metabolism; Survival Analysis; T cells; Transcription; Tumor necrosis factor-TNF; Viral infections; Viral Load; Viruses; West Nile virus; β-Interferon; γ-Interferon; encephalitis; herpes simplex virus 1; T cells; brain; interferon; microglia; PLX5622
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222212457

Herpes simplex virus 1 (HSV-1) infects the majority of the human population and can induce encephalitis, which is the most common cause of sporadic, fatal encephalitis. An increase of microglia is detected in the brains of encephalitis patients. The issues regarding whether and how microglia protect the host and neurons from HSV-1 infection remain elusive. Using a murine infection model, we showed that HSV-1 infection on corneas increased the number of microglia to outnumber those of infiltrating leukocytes (macrophages, neutrophils, and T cells) and enhanced microglia activation in brains. HSV-1 antigens were detected in brain neurons, which were surrounded by microglia. Microglia depletion increased HSV-1 lethality of mice with elevated brain levels of viral loads, infected neurons, neuron loss, CD4 T cells, CD8 T cells, neutrophils, interferon (IFN)-β, and IFN-γ. In vitro studies demonstrated that microglia from infected mice reduced virus infectivity. Moreover, microglia induced IFN-β and the signaling pathway of signal transducer and activator of transcription (STAT) 1 to inhibit viral replication and damage of neurons. Our study reveals how microglia protect the host and neurons from HSV-1 infection.