Trauma-induced heme release increases susceptibility to bacterial infection
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...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
American Society for Clinical Investigation
2023
|
| Online Access: | https://hdl.handle.net/1721.1/147024 |
| _version_ | 1826212914067931136 |
|---|---|
| author | 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 Hauser, Carl J Otterbein, Leo E |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology 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 Hauser, Carl J Otterbein, Leo E |
| author_sort | Lee, Ghee Rye |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T15:40:10Z |
| format | Article |
| id | mit-1721.1/147024 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T15:40:10Z |
| publishDate | 2023 |
| publisher | American Society for Clinical Investigation |
| record_format | dspace |
| spelling | mit-1721.1/1470242023-01-10T03:06:02Z Trauma-induced heme release increases susceptibility to bacterial infection 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 Hauser, Carl J Otterbein, Leo E Massachusetts Institute of Technology. Department of Biology 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. 2023-01-09T18:28:51Z 2023-01-09T18:28:51Z 2021 2023-01-09T18:16:00Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/147024 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). en 10.1172/JCI.INSIGHT.150813 JCI Insight Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf American Society for Clinical Investigation American Society for Clinical Investigation |
| spellingShingle | 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 Hauser, Carl J Otterbein, Leo E Trauma-induced heme release increases susceptibility to bacterial infection |
| title | Trauma-induced heme release increases susceptibility to bacterial infection |
| title_full | Trauma-induced heme release increases susceptibility to bacterial infection |
| title_fullStr | Trauma-induced heme release increases susceptibility to bacterial infection |
| title_full_unstemmed | Trauma-induced heme release increases susceptibility to bacterial infection |
| title_short | Trauma-induced heme release increases susceptibility to bacterial infection |
| title_sort | trauma induced heme release increases susceptibility to bacterial infection |
| url | https://hdl.handle.net/1721.1/147024 |
| work_keys_str_mv | AT leegheerye traumainducedhemereleaseincreasessusceptibilitytobacterialinfection AT gallodavid traumainducedhemereleaseincreasessusceptibilitytobacterialinfection AT alvesdesouzarodrigow traumainducedhemereleaseincreasessusceptibilitytobacterialinfection AT tiwarihecklershilpa traumainducedhemereleaseincreasessusceptibilitytobacterialinfection AT csizmadiaeva traumainducedhemereleaseincreasessusceptibilitytobacterialinfection AT harbisonjamesd traumainducedhemereleaseincreasessusceptibilitytobacterialinfection AT shankarsidharth traumainducedhemereleaseincreasessusceptibilitytobacterialinfection AT bannergoodspeedvalerie traumainducedhemereleaseincreasessusceptibilitytobacterialinfection AT yaffemichaelb traumainducedhemereleaseincreasessusceptibilitytobacterialinfection AT longhimariaserena traumainducedhemereleaseincreasessusceptibilitytobacterialinfection AT hausercarlj traumainducedhemereleaseincreasessusceptibilitytobacterialinfection AT otterbeinleoe traumainducedhemereleaseincreasessusceptibilitytobacterialinfection |