Microglia Reduce Herpes Simplex Virus 1 Lethality of Mice with Decreased T Cell and Interferon Responses in Brains
Autor: | Sheng Min Hsu, Li-Chiu Wang, Hsien-Yang Tsai, Yu-Jheng Lin, Meng-Shan Tsai, Shun-Fen Tzeng, Shun Hua Chen, Hua-Lin Wu |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
CD4-Positive T-Lymphocytes
Neutrophils viruses encephalitis microglia Cell Count Herpesvirus 1 Human CD8-Positive T-Lymphocytes medicine.disease_cause Cornea Mice Interferon Cytotoxic T cell Biology (General) Organic Chemicals Spectroscopy Neurons education.field_of_study Microglia General Medicine interferon Viral Load Computer Science Applications Chemistry medicine.anatomical_structure STAT1 Transcription Factor Female herpes simplex virus 1 Encephalitis medicine.drug Signal Transduction QH301-705.5 T cell brain Population T cells Biology Catalysis Virus Article Inorganic Chemistry Interferon-gamma medicine Animals Humans Physical and Theoretical Chemistry education Molecular Biology QD1-999 Macrophages Organic Chemistry Herpes Simplex Interferon-beta medicine.disease Virology Survival Analysis Mice Inbred C57BL PLX5622 Disease Models Animal Herpes simplex virus nervous system Gene Expression Regulation |
Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 22 International Journal of Molecular Sciences, Vol 22, Iss 12457, p 12457 (2021) |
ISSN: | 1422-0067 |
Popis: | 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. |
Databáze: | OpenAIRE |
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