Trauma-induced heme release increases susceptibility to bacterial infection
Name
150813.2-20211008101822-covered-e0fd13ba177f913fd3156f593ead4cfd.pdf
Description
Published version
Size
1.85 MB
Format
Adobe PDF
Checksum (MD5)
5ec4360231754eb50d84d8d8a517c016
Author(s)
Lee, Ghee Rye
Gallo, David
Alves de Souza, Rodrigo W
Tiwari-Heckler, Shilpa
Csizmadia, Eva
Harbison, James D
Shankar, Sidharth
Banner-Goodspeed, Valerie
Yaffe, Michael B
Longhi, Maria Serena
Date Issued
2021
Journal
JCI Insight
Publisher
American Society for Clinical Investigation
Citation
Lee, Ghee Rye, Gallo, David, Alves de Souza, Rodrigo W, Tiwari-Heckler, Shilpa, Csizmadia, Eva et al. 2021. "Trauma-induced heme release increases susceptibility to bacterial infection." JCI Insight, 6 (20).
Version
Final published version
Abstract
Infection is a common complication of major trauma that causes significantly increased morbidity and mortality. The mechanisms, however, linking tissue injury to increased susceptibility to infection remain poorly understood. To study this relationship, we present a potentially novel murine model in which a major liver crush injury is followed by bacterial inoculation into the lung. We find that such tissue trauma both impaired bacterial clearance and was associated with significant elevations in plasma heme levels. While neutrophil (PMN) recruitment to the lung in response to Staphylococcus aureus was unchanged after trauma, PMN cleared bacteria poorly. Moreover, PMN show > 50% less expression of TLR2, which is responsible, in part, for bacterial recognition. Administration of heme effectively substituted for trauma. Finally, day 1 trauma patients (n = 9) showed similar elevations in free heme compared with that seen after murine liver injury, and circulating PMN showed similar TLR2 reduction compared with volunteers (n = 6). These findings correlate to high infection rates.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1172/JCI.INSIGHT.150813
