Abstract
The cerebral immune response induced by herpes simplex virus (HSV) encephalitis (HSE) was evaluated in susceptible BALB/c and resistant C57BL/6 mice. BALB/c and C57BL/6 (named C57BL/6-high) mice were respectively infected intranasally with 1 × 103 and 5 × 105 plaque-forming units (PFUs) of HSV-1. C57BL/6 mice (named C57BL/6-low) infected with a low inoculum (1 × 103 PFUs) of HSV-1 were tested in parallel. Mice were monitored for weight loss, sickness signs, and survival for 21 days. The viral load, infectious titers, cytokine/chemokine levels, and peripheral leukocyte infiltration were determined in brain homogenates on days 0 (non-infected), 4, 6, and 8 post-infection (p.i.) by qPCR, plaque assay, ELISA/Luminex™, and flow cytometry, respectively. Our results showed that the mortality of BALB/c mice (67%) was higher compared to those of C57BL/6-low (0%; P ≤ 0.01) and C57BL/6-high (20%; P ≤ 0.05) animals. This higher mortality was associated with increased infectious titers and cytokine/chemokine levels in the brains of BALB/c compared to C57BL/6 mice. Recruitment of inflammatory monocytes, dendritic cells, natural killer, and natural killer T cells to the brain was higher in C57BL/6-high compared to BALB/c animals on day 4 p.i. Infiltration of inflammatory monocytes and T cells in the brain of BALB/c mice was seen on day 6 p.i. Our data suggest that a rapid, sustained, and coordinated recruitment of peripheral leukocytes to the brain of C57BL/6-high mice results in an effective control of viral replication and inflammation whereas the delayed infiltration of immune cells in the brain of BALB/c mice was associated with an exacerbated inflammatory response during HSE.
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Acknowledgments
The authors would like to thank Julie-Christine Levesque from Luminex technology platform of Research Center of the CHU of Quebec-Laval University for assistance in Bio-Plex system and Bio-Plex manager software as well as Alexandre Brunet from Imaging and Cytometry platforms of Research Center of the CHU of Quebec-Laval University for assistance in acquisition of flow cytometry data.
Funding
This study was supported by a Foundation Grant from the Canadian Institutes of Health Research (grant no. 148361 to G.B.). G.B. is the holder of the Canada research chair on emerging viruses and antiviral resistance.
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Canivet, C., Uyar, O., Rhéaume, C. et al. The recruitment of peripheral blood leukocytes to the brain is delayed in susceptible BALB/c compared to resistant C57BL/6 mice during herpes simplex virus encephalitis. J. Neurovirol. 25, 372–383 (2019). https://doi.org/10.1007/s13365-019-00730-5
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DOI: https://doi.org/10.1007/s13365-019-00730-5