Molecular profiles of blood from numerous species that differ in sensitivity to acute inflammation
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.
Authors
- Ronald G. Tompkins (ORCID: https://orcid.org/0000-0002-0859-526X)
- Renata Sindeaux (ORCID: https://orcid.org/0000-0002-5527-5015)
- Wenzhong Xiao (ORCID: https://orcid.org/0000-0003-4944-6380)
- Feifei Han (ORCID: https://orcid.org/0000-0003-4373-8753)
- Jennifer Kyle (ORCID: https://orcid.org/0000-0002-9282-9005)
- Frank E. Riley
- Mohamed B. F. Hawash (ORCID: https://orcid.org/0000-0001-6538-2052)
- Vania Yotova (ORCID: https://orcid.org/0000-0002-6730-2404)
- Li-Yuan Hung (ORCID: https://orcid.org/0000-0002-0442-5829)
- Lester Kobzik (ORCID: https://orcid.org/0000-0003-4328-937X)
- David J. Gregory (ORCID: https://orcid.org/0000-0001-6534-7150)
- Jon Jacobs (ORCID: https://orcid.org/0000-0003-0557-7338)
- Judith Hellman (ORCID: https://orcid.org/0000-0003-2278-6625)
- Marina Gritsenko (ORCID: https://orcid.org/0000-0001-9992-9829)
- H. Shaw Warren (ORCID: https://orcid.org/0009-0005-1128-7056)
- Ivor S. Douglas (ORCID: https://orcid.org/0000-0002-4541-1431)
- Robert E. Lanford (ORCID: https://orcid.org/0000-0003-4980-2920)
- Deborah Chavez (ORCID: https://orcid.org/0000-0003-4403-0343)
- Luis B. Barreiro (ORCID: https://orcid.org/0000-0001-9456-367X)
- Peng Li (ORCID: https://orcid.org/0000-0003-4530-2400)
- Fengyun Xu
Institutions
- Texas Biomedical Research Institute (US)
- Harvard University (US)
- Pacific Northwest National Laboratory (US)
- University of California, San Francisco (US)
- Hospital for Sick Children (CA)
- Centre Hospitalier Universitaire Sainte-Justine (CA)
- University of Chicago (US)
- Massachusetts General Hospital (US)
- Université de Montréal (CA)
Publication Details
- Journal
- Molecular Medicine
- Published
- 2024-12-28
- DOI
- https://doi.org/10.1186/s10020-024-01052-x
- Citations
- 6
- Primary Topic
- Immune Response and Inflammation
- Type
- article
- Field-Weighted Citation Impact
- 1.44
Funders
- U.S. Department of Energy
- Open Medicine Foundation
- National Institutes of Health
- Defense Advanced Research Projects Agency