Biological Sciences Division
Published December 28, 2024 | Version v1
Journal article Open

Molecular profiles of blood from numerous species that differ in sensitivity to acute inflammation

Creators

  • 1. Massachusetts General Hospital
  • 2. Harvard University
  • 3. Pacific Northwest National Laboratory
  • 4. Texas Biomedical Research Institute
  • 5. Centre Hospitalier Universitaire Sainte-Justine
  • 6. Hospital for Sick Children
  • 7. University of California, San Francisco
  • 8. University of Chicago

Description

Vertebrates differ over 100,000-fold in responses to pro-inflammatory agonists such as bacterial lipopolysaccharide (LPS), complicating use of animal models to study human sepsis or inflammatory disorders. We compared transcriptomes of resting and LPS-exposed blood from six LPS-sensitive species (rabbit, pig, sheep, cow, chimpanzee, human) and four LPS-resilient species (mice, rats, baboon, rhesus), as well as plasma proteomes and lipidomes. Unexpectedly, at baseline, sensitive species already had enhanced expression of LPS-responsive genes relative to resilient species. After LPS stimulation, maximally different genes in resilient species included genes that detoxify LPS, diminish bacterial growth, discriminate sepsis from SIRS, and play roles in autophagy and apoptosis. The findings reveal the molecular landscape of species differences in inflammation. This may inform better selection of species for pre-clinical models and could lead to new therapeutic strategies that mimic mechanisms in inflammation-resilient species to limit inflammation without causing immunosuppression.

Data availability

RNAseq data related to this study has been deposited in GEO, Accession GSE249010. Processed data will be shared on reasonable request to the corresponding authors.

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Additional details

Identifiers

DOI
10.1186/s10020-024-01052-x
Other
oai:uchicago.tind.io:14328

Funding

Defense Advanced Research Projects Agency
15–21-THoR-FP-007
U.S. Army
W911NF-16C-0079
National Institutes of Health
Office of Research Infrastructure Programs/Office of the Director
National Institutes of Health
Office of Research Infrastructure Programs/Office of the Director
National Institutes of Health
NIGMS GM103493

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Human Genetics, Immunology, Medicine