Single‑cell transcriptomics of the ventral posterolateral nucleus‑enriched thalamic regions from HSV‑1‑infected mice reveal a novel microglia/microglia‑like transcriptional response

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dc.contributor.authorUyar, Olus
dc.contributor.authorDominguez, Juan Manuel
dc.contributor.authorBordeleau, Maude
dc.contributor.authorLapeyre, Lina
dc.contributor.authorGonzález Ibáñez, Fernando
dc.contributor.authorVallières, Luc
dc.contributor.authorTremblay, Marie-Ève
dc.contributor.authorCorbeil, Jacques
dc.contributor.authorBoivin, Guy
dc.date.accessioned2024-02-02T19:49:29Z
dc.date.available2024-02-02T19:49:29Z
dc.date.copyright2022en_US
dc.date.issued2022
dc.descriptionWe want to thank Stéphane Dubois, Annie-Claude Collin-Deschesnes and Dr. Martine Dumont from the genomics center for sample management and skillful technical assistance, Julie-Christine Levesque for her technical assistance with confocal microscopy, Dr. Emilie Pic from Dr. Jacques Corbeil lab for her contributions to the coordination of this study, Dr. Elsa Rousseau for her technical advises, Dr. Marc Bazin from Dr. Girish Shah lab for his technical support in IVIS Lumina III (PerkinElmer); all are located at the CHU de Québec-Laval University Research Center.en_US
dc.description.abstractBackground: Microglia participate in the immune response upon central nervous system (CNS) infections. However, the role of these cells during herpes simplex encephalitis (HSE) has not been fully characterized. We sought to identify different microglia/microglia-like cells and describe the potential mechanisms and signaling pathways involved during HSE. Methods: The transcriptional response of CD11b+ immune cells, including microglia/microglia-like cells, was investigated using single-cell RNA sequencing (scRNA-seq) on cells isolated from the ventral posterolateral nucleus (VPL)-enriched thalamic regions of C57BL/6 N mice intranasally infected with herpes simplex virus-1 (HSV-1) (6 × 105 PFUs/20 μl). We further performed scanning electronic microscopy (SEM) analysis in VPL regions on day 6 post-infection (p.i.) to provide insight into microglial functions. Results: We describe a novel microglia-like transcriptional response associated with a rare cell population (7% of all analyzed cells), named “in transition” microglia/microglia-like cells in HSE. This new microglia-like transcriptional signature, found in the highly infected thalamic regions, was enriched in specific genes (Retnlg, Cxcr2, Il1f9) usually associated with neutrophils. Pathway analysis of this cell-type transcriptome showed increased NLRP3-inflammasomemediated interleukin IL-1β production, promoting a pro-inflammatory response. These cells’ increased expression of viral transcripts suggests that the distinct “in transition” transcriptome corresponds to the intrinsic antiviral immune signaling of HSV-1-infected microglia/microglia-like cells in the thalamus. In accordance with this phenotype, we observed several TMEM119+/IBA-I+ microglia/microglia-like cells immunostained for HSV-1 in highly infected regions. Conclusions: A new microglia/microglia-like state may potentially shed light on how microglia could react to HSV-1 infection. Our observations suggest that infected microglia/microglia-like cells contribute to an exacerbated CNSen_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipTwo Grants from the Canadian Institutes of Health Research (Grant no. 148361 to G.B. and Grant no. 143279 to J.C.) supported this study. G.B. is the holder of the Canada Research Chair (CRC) on emerging viruses and antiviral resistance and MET of the CRC in Neurobiology of Aging and Cognition, J.C. holds a CRC in Medical Genomics (950-231574). FGI is a holder of a doctoral scholarship by the Mexican Council of Science and Technology (CONACYT). MB was a holder of the doctoral FRQS award during part of this study.en_US
dc.identifier.citationUyar, O., Dominguez, J. M., Bordeleau, M., Lapeyre, L., González Ibáñez, F., Vallières, L., ... Boivin, G. (2022). Single‑cell transcriptomics of the ventral posterolateral nucleus‑enriched thalamic regions from HSV‑1‑infected mice reveal a novel microglia/microglia‑like transcriptional response. Journal of Neuroinflammation, 19(81). https://doi.org/10.1186/s12974-022-02437-7en_US
dc.identifier.urihttps://doi.org/10.1186/s12974-022-02437-7
dc.identifier.urihttp://hdl.handle.net/1828/15920
dc.language.isoenen_US
dc.publisherJournal of Neuroinflammationen_US
dc.subjectHerpes simplex virus 1
dc.subjectEncephalitis
dc.subjectTranscriptomics
dc.subjectAntiviral immune response
dc.subjectMicroglia
dc.subjectCentre for Advanced Materials and Related Technology (CAMTEC)
dc.subject.departmentDivision of Medical Sciences
dc.subject.departmentSchool of Medical Sciences
dc.titleSingle‑cell transcriptomics of the ventral posterolateral nucleus‑enriched thalamic regions from HSV‑1‑infected mice reveal a novel microglia/microglia‑like transcriptional responseen_US
dc.typeArticleen_US

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