Influenza A virus infection disrupts oligodendrocyte homeostasis and alters the myelin lipidome in the adult mouse

Journal of Neuroinflammation

Research

Payam Dibaeinia¹  Romana A. Nowak²  Hisami Koito³  Saurabh Sinha⁴  Justin S. Kim⁵  Katiria Soto-Diaz⁶  Allison Y. Louie⁶  Andrew J. Steelman⁷  Daniel B. McKim⁸  Aditi Das⁹  Jenny Drnevich^1,10 

[1] Department of Computer Science, University of Illinois at Urbana-Champaign, 201 North Goodwin Avenue, 61801, Urbana, IL, USA;Department of Computer Science, University of Illinois at Urbana-Champaign, 201 North Goodwin Avenue, 61801, Urbana, IL, USA;Department of Bioengineering, Cancer Center at Illinois, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, 405 N. Mathews Ave., 61801, Urbana, IL, USA;Department of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado-shi, 350-0295, Saitama, Japan;Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 1201 W. Gregory Dr., 61801, Urbana, IL, USA;Department of Computer Science, University of Illinois at Urbana-Champaign, 201 North Goodwin Avenue, 61801, Urbana, IL, USA;Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 West Gregory Dr., 61801, Urbana, IL, USA;The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, USA;Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 1201 W. Gregory Dr., 61801, Urbana, IL, USA;School of Chemistry and Biochemistry, Georgia Institute of Technology, 3306, IBB, Parker H. Petit Institute for Bioengineering and Biosciences, 315 Fernst Dr. NW, 30332, Atlanta, GA, USA;Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, 3516 Veterinary Medicine Basic Sciences Bldg., 2001 South Lincoln Avenue, 61802, Urbana, IL, USA;Neuroscience Program, 2325/21 Beckman Institute, 405 North Mathews Ave., 61801, Urbana, IL, USA;Neuroscience Program, 2325/21 Beckman Institute, 405 North Mathews Ave., 61801, Urbana, IL, USA;Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 1201 W. Gregory Dr., 61801, Urbana, IL, USA;Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 West Gregory Dr., 61801, Urbana, IL, USA;Department of Bioengineering, Cancer Center at Illinois, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, 405 N. Mathews Ave., 61801, Urbana, IL, USA;Neuroscience Program, 2325/21 Beckman Institute, 405 North Mathews Ave., 61801, Urbana, IL, USA;Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 1201 W. Gregory Dr., 61801, Urbana, IL, USA;Department of Animal Sciences, University of Illinois at Urbana-Champaign, 1201 W. Gregory Dr., 61801, Urbana, IL, USA;Neuroscience Program, 2325/21 Beckman Institute, 405 North Mathews Ave., 61801, Urbana, IL, USA;Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 1201 W. Gregory Dr., 61801, Urbana, IL, USA;School of Chemistry and Biochemistry, Georgia Institute of Technology, 3306, IBB, Parker H. Petit Institute for Bioengineering and Biosciences, 315 Fernst Dr. NW, 30332, Atlanta, GA, USA;Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, 3516 Veterinary Medicine Basic Sciences Bldg., 2001 South Lincoln Avenue, 61802, Urbana, IL, USA;Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 West Gregory Dr., 61801, Urbana, IL, USA;Roy J. Carver Biotechnology Center, University of Illinois at Urbana-Champaign, Urbana, IL, USA;

关键词: Myelin;    Myelin plasticity;    Lipid;    Lipidome;    Microglia;    Oligodendrocyte;    Influenza virus;    Inflammation;    Systemic inflammation;   

DOI  :  10.1186/s12974-023-02862-2

 received in 2023-02-11, accepted in 2023-07-25,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundRecent data suggest that myelin may be altered by physiological events occurring outside of the central nervous system, which may cause changes to cognition and behavior. Similarly, peripheral infection by non-neurotropic viruses is also known to evoke changes to cognition and behavior.MethodsMice were inoculated with saline or influenza A virus. Bulk RNA-seq, lipidomics, RT-qPCR, flow cytometry, immunostaining, and western blots were used to determine the effect of infection on OL viability, protein expression and changes to the lipidome. To determine if microglia mediated infection-induced changes to OL homeostasis, mice were treated with GW2580, an inhibitor of microglia activation. Additionally, conditioned medium experiments using primary glial cell cultures were also used to test whether secreted factors from microglia could suppress OL gene expression.ResultsTranscriptomic and RT-qPCR analyses revealed temporal downregulation of OL-specific transcripts with concurrent upregulation of markers characteristic of cellular stress. OLs isolated from infected mice had reduced cellular expression of myelin proteins compared with those from saline-inoculated controls. In contrast, the expression of these proteins within myelin was not different between groups. Similarly, histological and immunoblotting analysis performed on various brain regions indicated that infection did not alter OL viability, but increased expression of a cellular stress marker. Shot-gun lipidomic analysis revealed that infection altered the lipid profile within the prefrontal cortex as well as in purified brain myelin and that these changes persisted after recovery from infection. Treatment with GW2580 during infection suppressed the expression of genes associated with glial activation and partially restored OL-specific transcripts to baseline levels. Finally, conditioned medium from activated microglia reduced OL-gene expression in primary OLs without altering their viability.ConclusionsThese findings show that peripheral respiratory viral infection with IAV is capable of altering OL homeostasis and indicate that microglia activation is likely involved in the process.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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