SARS-CoV-2 infection elicits robust CD8 T-cell responses, yet the identity of the mechanisms playing dominant roles in initiating the virus-specific CD8 T-cell responses are largely unknown. In the present study, we interrogate the contribution of the cDC1 subset to SARS-CoV-2-specific CD8 T-cell immunity. For this purpose, we used a novel murine line which combines the SARS-CoV-2 susceptible K18-hACE2 transgenic and the Batf3 deficient mice which lack the cDC1 subset. We demonstrate that in the absence of cDC1, viral-specific CD8 T-cell responses were severely impaired both in the draining lymph node as well as in the lungs, during the effector phase of SARS-CoV-2 infection. Furthermore, SARS-CoV-2 specific memory CD8 T-cells in the lungs and spleens were also significantly impacted, whereas humoral responses, as well as CD4 T-cells were not affected. Additionally, we demonstrate that the absence of cDC1 subset, and the consequent impaired CD8 T-cell responses, resulted in significant increase in SARS-CoV-2 viral load in the lungs. The conclusions of the study were further independently corroborated in an additional COVID-19 murine model consisting infection with a mouse-adapted SARS-CoV-2 virus. These results underscore a specific role for Batf3-dependent DC in regulating SARS-CoV-2 specific CD8 T-cell responses and may contribute to future vaccine design and immunization strategies.
Copyright: © 2023 Bar-On et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.