Dermal fibroblast cultures recapitulate differences between deermice and mice in their responses to a Toll-like receptor agonist.

Introduction: The white-footed deermouse Methods: As an approach for assessing immunity of mammals in nature and for longitudinal studies of colony animals in the laboratory, we evaluated primary dermal fibroblast cultures of Results: By single-cell RNA-seq, cultures of both species comprised at least two types of fibroblasts, which were further differentiated in their responses to TLR agonists. With continued passage, the mouse cell population lost viability, while the deermouse cell population spontaneously transformed into a cell line stably maintained under standard conditions. Bulk RNA-seq revealed distinctive profiles for deermouse and mouse cells in arginine metabolism gene expression, high baseline transcription of the antioxidant transcription factor Nfe2l2 (Nrf2) in deermouse fibroblasts, and the transcription of the aging-associated cytokine interleukin-11 in agonist-treated mouse fibroblasts but not deermouse fibroblasts. In the cultures of both species, there was increased transcription of several types of endogenous retrovirus (ERV) and transposable elements (TEs) after exposure to the agonist. The transcribed ERV/TE sequences in Discussion: The results indicate the feasibility of this in vitro model for both laboratory- and field-based studies, and that inherent differences between deer mice and mice in cell-autonomous innate immune responses and ERV/TE activation can be demonstrated in dermal fibroblasts as well as the animals themselves.