Multi-Omic blood analysis reveals differences in innate inflammatory sensitivity between species

Area of Science:

• Comparative genomics
• Immunology
• Translational medicine

Background:

• Vertebrate responses to pro-inflammatory agonists like bacterial lipopolysaccharide (LPS) vary significantly, complicating the use of animal models for human sepsis and inflammatory diseases.
• Understanding these species-specific differences is crucial for selecting appropriate preclinical models.

Approach:

• Comparative transcriptomic, proteomic, and lipidomic analyses were performed on blood samples from LPS-sensitive (rabbit, pig, sheep, cow, chimpanzee, human) and LPS-resilient (mice, rats, baboon, rhesus) species.
• Samples were analyzed at baseline (resting) and after LPS stimulation.

Key Points:

• LPS-sensitive species exhibited higher baseline expression of LPS-responsive genes compared to LPS-resilient species.
• Following LPS stimulation, LPS-resilient species upregulated genes involved in LPS detoxification, bacterial growth inhibition, sepsis/SIRS discrimination, autophagy, and apoptosis.
• Significant molecular differences exist between species in their inflammatory responses.

Conclusions:

• The study reveals the molecular basis for species differences in inflammation and LPS response.
• Findings provide insights into selecting optimal animal models for preclinical studies of sepsis and inflammatory disorders.
• Understanding baseline gene expression and post-stimulation pathways is key to interpreting animal model data.