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

• Published in: eLife 2024-01, Vol.12
• Main Authors: Milovic, Ana, Duong, Jonathan V, Barbour, Alan G
• Format: Article
• Language: English
• Subjects: Anaplasmosis; Animals; Babesiosis; Blood; Disease; Encephalitis; endogenous retrovirus; Endotoxins; Females; Genomes; Genotype & phenotype; Humans; Immunology and Inflammation; Infections; Inflammation; Interferon Type I; Interferon-gamma; interferons; lipopolysaccharide; Lipopolysaccharides; Lyme disease; Macrophages; Mice; Microbiology and Infectious Disease; Monocytes; Neutrophils; Pattern recognition receptors; Peromyscus; Rats; Transcription; Zoonoses; γ-Interferon
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.90135

The white-footed deermouse , 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 , and 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 , 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 were also noted in a 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.