Sequential early life infections alter peripheral blood transcriptomics in aging female mice but not the response to de novo infection with influenza virus or M. tuberculosis

ABSTRACT: The experimental mouse model is important for understanding the impact of aging on immune function. Humans are exposed to multiple pathogens during their lifetime, which has a significant effect on immune function as they age, while laboratory mice are aged under specific pathogen-free (SPF) conditions, reducing their exposure to pathogens throughout life. To determine the impact of accumulating antigen exposure on immunity in the aging mouse, and to develop a more relevant model, we sequentially infected young female mice with four distinct pathogens, a murine g-herpesvirus (gHV68), Sendai virus, murine cytomegalovirus (mCMV) and Heligmosomoides polygyrus (H. poly) at eight-week intervals, while mock-infected mice received PBS. After aging the mice to 18-20 months, we analyzed multiple immune parameters, compared to control, mock-infected mice maintained under SPF conditions. We assessed transcriptional activity in peripheral blood, T cell phenotype, CD8 T cell repertoire, and the response of the animals to infection with influenza virus and M. tuberculosis. Our data show enhanced transcriptional activation in sequentially infected aged mice, with changes in some CD8 T cell subsets. However, there was no measurable difference in the response of mock and sequentially infected aged mice to de novo infection with either influenza virus or M. tuberculosis at 18-20 months. Unexpectedly, undertaking a similar influenza challenge in 25-month-old female mice revealed a significantly higher survival rate for serially infected (80%) versus mock infected (20%) mice. These data suggest that while exposure to a variety of pathogen challenges in the mouse model does not overtly impact cellular markers of immunity in aged female mice following de novo respiratory infection, subtle changes may emerge in other compartments or with increasing age.

ORGANISM(S): Mus musculus

PROVIDER: GSE199730 | GEO | 2023/07/10

REPOSITORIES: GEO