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

Date

2022

Authors

Uyar, Olus
Dominguez, Juan Manuel
Bordeleau, Maude
Lapeyre, Lina
González Ibáñez, Fernando
Vallières, Luc
Tremblay, Marie-Eve
Corbeil, Jacques
Boivin, Guy

Journal Title

Journal ISSN

Volume Title

Publisher

Journal of Neuroinflammation

Abstract

Background: 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 CNS

Description

We 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.

Keywords

Herpes simplex virus 1, Encephalitis, Transcriptomics, Antiviral immune response, Microglia

Citation

Uyar, 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/s12974-022-02437-7