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Detection of disease-associated microglia among various microglia phenotypes induced by West Nile virus infection in mice

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Abstract

West Nile virus (WNV) has emerged as a significant cause of viral encephalitis in humans and horses. However, the pathogenesis of the West Nile encephalitis remains unclear. Microglia are activated by WNV infection, and the pathogenic involvement of their phenotypes is controversial. In this study, we examined the diversity of microglia phenotypes caused by WNV infection by assessing various microglia markers and identified disease-associated microglia in WNV-infected mouse brain tissue. Cells positive for general microglia markers such as Iba1, P2RY12, or TMEM119 were detected in the control and WNV-infected brain tissue. The morphology of the positive cells in brain tissue infected by WNV was different from that of control brain tissue, indicating that WNV infection induced activation of microglia. The activated microglia were classified into various phenotypes by investigation of specific marker expression. Among the activated microglia, disease-associated microglia that were positive for CD11c and weakly positive for TMEM119 were detected close to the WNV-infected cells. These results indicate that WNV infection induces activation of diverse microglia phenotypes and that disease-associated microglia may be associated with the pathogenicity of WNV infection in the mouse brain.

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The data is available upon request.

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Acknowledgements

We would like to acknowledge the help of all members in the Laboratory of Public Health, Faculty of Veterinary Medicine, Hokkaido University.

Funding

This work was supported in part by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number, 20K06406; the Research Program on Emerging and Re-emerging Infectious Diseases from Japan Agency for Medical Research and Development, AMED (JP21fk0108567h0001 and JP223fa627005); Takeda Science Foundation; MSD Life Science Foundation, Public Interest Incorporated Foundation; The Akiyama Life Science Foundation; Grant for Joint Research Program of the Institute for Genetic Medicine, Hokkaido University; the cooperative research project program of the National Research Center for the Control and Prevention of Infectious Diseases, Nagasaki University; JST SPRING (JPMJSP2119); and the World-leading Innovative and Smart Education (WISE) Program (1801) from the Ministry of Education, Culture, Sports, and Technology, Japan.

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Authors and Affiliations

  1. Laboratory of Public Health, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan

    Passawat Thammahakin, Keisuke Maezono, Hiroaki Kariwa & Shintaro Kobayashi

  2. Department of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan

    Naoya Maekawa

  3. Institute for Vaccine Research and Development (HU-IVReD), Hokkaido University, Sapporo, Japan

    Shintaro Kobayashi

Authors
  1. Passawat Thammahakin
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  2. Keisuke Maezono
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  3. Naoya Maekawa
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  4. Hiroaki Kariwa
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  5. Shintaro Kobayashi
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Contributions

Conceptualization: Passawat Thammahakin and Shintaro Kobayashi; methodology: Passawat Thammahakin, Keisuke Maezono, Naoya Maekawa, and Shintaro Kobayashi; formal analysis and investigation: Passawat Thammahakin and Shintaro Kobayashi; writing—original draft preparation: Passawat Thammahakin and Shintaro Kobayashi; writing—review and editing: Hiroaki Kariwa and Shintaro Kobayashi; and supervision: Hiroaki Kariwa and Shintaro Kobayashi.

Corresponding author

Correspondence to Shintaro Kobayashi.

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Ethics statement

All animal experiments were performed following the basic guideline for animal experiments of the Ministry of Education, Culture, Sport, Science and Technology (MEXT), Japan. The President of Hokkaido University approved all animal experiments after review by the Institutional Animal Care and Use Committee of Hokkaido University (approval no. 19-0142).

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Thammahakin, P., Maezono, K., Maekawa, N. et al. Detection of disease-associated microglia among various microglia phenotypes induced by West Nile virus infection in mice. J. Neurovirol. 29, 367–375 (2023). https://doi.org/10.1007/s13365-023-01161-z

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  • DOI: https://doi.org/10.1007/s13365-023-01161-z

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