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

Ana Milovic | Jonathan V Duong | Alan G Barbour
eLife | 2024

The white-footed deermouse Peromyscus leucopus, 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 P. leucopus, Mus musculus, and Rattus norvegicus 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 P. leucopus, 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 P. leucopus were also noted in a Borrelia hermsii 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.

Pubmed ID: 38193896

Associated grants

  • Agency: NIH HHS, United States
    Id: S10 OD021718
  • Agency: NIH HHS, United States
    Id: AI136523
  • Agency: NIH HHS, United States
    Id: S10 OD010794
  • Agency: NIAID NIH HHS, United States
    Id: R21 AI136523
  • Agency: NCRR NIH HHS, United States
    Id: S10 RR025496
  • Agency: NIH HHS, United States
    Id: AI157513
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI157513
  • Agency: NCI NIH HHS, United States
    Id: P30 CA062203

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RRID:SCR_012773

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