Comprehensive single-cell profiling of T and B cell subsets in mice reveals impacts on memory immune responses in FMDV infection

Abstract

The impact of Foot-and-Mouth Disease Virus (FMDV) on memory immune responses has not been thoroughly investigated due to limited availability of immunological research tools. Using single-cell RNA sequencing, we identified specific gene markers for the majority of T and B cell subsets in the spleens of mice. Our findings indicate that FMDV infection significantly reduces the proportions of memory cell populations (e.g., memory B cells, memory CD4⁺ T cells, and memory CD8⁺ T cells) relative to their respective lymphocyte subsets (total B cells, CD4⁺ T cells, and CD8⁺ T cells) in the short term, impacting their functions. These alterations largely reverse over the long term. Specifically, FMDV infection primarily exerts its impacts on the function of memory cells by enhancing key immunological functions such as activation, proliferation, differentiation, and polarization, while simultaneously suppressing essential cellular biological functions including proliferation and metabolism. These impacts were significantly associated with Fos-related genes. Our study provides new insights into the immune evasion mechanisms of FMDV, establishes adult mice as potential models for FMDV immunological research, and offers valuable tools for single-cell RNA sequencing in murine immunological studies.