The infection-tolerant white-footed deermouse tempers interferon responses to endotoxin in comparison to the mouse and rat.

Abstract

The white-footed deermouse <i>Peromyscus leucopus</i>, a long-lived rodent, is a key reservoir in North America for agents of several zoonoses, including Lyme disease, babesiosis, anaplasmosis, and a viral encephalitis. While persistently infected, this deermouse is without apparent disability or diminished fitness. For a model for inflammation elicited by various pathogens, the endotoxin lipopolysaccharide (LPS) was used to compare genome-wide transcription in blood by <i>P. leucopus</i>, <i>Mus musculus,</i> and <i>Rattus norvegicus</i> and adjusted for white cell concentrations. Deermice were distinguished from the mice and rats by LPS response profiles consistent with non-classical monocytes and alternatively-activated macrophages. LPS-treated <i>P. leucopus</i>, in contrast to mice and rats, also displayed little transcription of interferon-gamma and lower magnitude fold-changes in type 1 interferon-stimulated genes. These characteristics of <i>P. leucopus</i> were also noted in a <i>Borrelia hermsii</i> infection model. The phenomenon was associated with comparatively reduced transcription of endogenous retrovirus sequences and cytoplasmic pattern recognition receptors in the deermice. The results reveal a mechanism for infection tolerance in this species and perhaps other animal reservoirs for agents of human disease.