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Trauma-induced heme release increases susceptibility to bacterial infection
Ghee Rye Lee, … , Carl J. Hauser, Leo E. Otterbein
Ghee Rye Lee, … , Carl J. Hauser, Leo E. Otterbein
Published September 14, 2021
Citation Information: JCI Insight. 2021;6(20):e150813. https://doi.org/10.1172/jci.insight.150813.
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Research Article Infectious disease Inflammation

Trauma-induced heme release increases susceptibility to bacterial infection

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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.

Authors

Ghee Rye Lee, David Gallo, Rodrigo W. Alves de Souza, Shilpa Tiwari-Heckler, Eva Csizmadia, James D. Harbison, Sidharth Shankar, Valerie Banner-Goodspeed, Michael B. Yaffe, Maria Serena Longhi, Carl J. Hauser, Leo E. Otterbein

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Figure 6

Trauma injury downregulates CD16, TLR2, and TLR4 expression in circulating PMN in patients.

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Trauma injury downregulates CD16, TLR2, and TLR4 expression in circulati...
(A–D) MFI of CD16, TLR2, TLR4, and CD66b in circulating PMN collected from control patients (n = 6) and trauma patients on day 0 or 1 (n = 9) measured by flow cytometry. A representative flow cytometry analysis image is shown on the right (except for CD66b). Gray represents unstained cells, blue the control, and red the trauma. All data are presented as mean ± SEM. Statistical analysis was performed by using unpaired 2-tailed Student’s t test. *P < 0.05, **P < 0.01.

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