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Increased MerTK expression in circulating innate immune cells of patients with septic shock
Caroline Guignant1, Fabienne Venet, Séverine Planel
1Laboratoire d'Immunologie, Hôpital E. Herriot, Hospices Civils de Lyon, 5 place d'Arsonval, 69437, Lyon cedex 03, France.
Purpose:
A new pathway of three protein tyrosine kinase receptors, namely, the TAM receptor family [Tyro-3, Axl and Mer tyrosine kinase (MerTK)], has recently been described to negatively control immune responses. The objective of this prospective, observational, clinical study was to investigate the expression patterns of TAM receptors in circulating white blood cells collected from patients with septic shock.
Methods:
The expression of TAM receptors was measured by flow cytometry in circulating leukocytes from patients with septic shock sampled on days (D) 1-2 (n = 47) and D3-4 (n = 37) after the onset of shock, severe trauma patients at D1-2 after trauma (n = 51) and healthy individuals (n = 23).
Results:
On D1-2 after injury, MerTK was overexpressed in monocytes and neutrophils collected from patients with septic shock in comparison with those collected from healthy volunteers and trauma patients. This phenomenon was also observed for mRNA. Conversely, the expression of Tyro-3 and Axl was higher in monocytes from trauma patients versus healthy volunteers or those in septic shock. MerTK expression between D1-2 and D3-4 remained elevated in patients suffering from septic shock who died or developed an intensive care unit-acquired infection, whereas it decreased in patients who recovered uneventfully. This in vivo observed expression pattern was reproduced ex vivo after the incubation of healthy volunteer cells with plasma from septic shock or trauma patients.
Conclusions:
MerTK expression in circulating innate immune cells is increased in patients with septic shock in comparison with healthy volunteers and trauma patients. Persistent MerTK overexpression after septic shock is associated with adverse outcome. The role of this family of receptors in the pathophysiology of injury-induced immune dysfunctions deserves to be specifically investigated.
Insights
MerTK, a key immune regulator, is overexpressed in septic shock patients, indicating a poor prognosis. This TAM receptor family member
Area of Science:
- Immunology
- Molecular Biology
- Critical Care Medicine
Background:
- The TAM receptor family (Tyro-3, Axl, MerTK) negatively regulates immune responses.
- Understanding TAM receptor roles is crucial in immune dysfunctions.
Purpose of the Study:
- To investigate TAM receptor expression patterns in white blood cells of septic shock patients.
- To correlate expression with clinical outcomes.
Main Methods:
- Prospective, observational clinical study.
- Flow cytometry analysis of TAM receptors (Tyro-3, Axl, MerTK) in leukocytes.
- Comparison between septic shock, trauma patients, and healthy individuals.
Main Results:
- MerTK was overexpressed in monocytes and neutrophils of septic shock patients compared to controls.
- Tyro-3 and Axl expression differed between trauma and septic shock groups.
- Persistent MerTK overexpression correlated with adverse outcomes (mortality, infection).
Conclusions:
- MerTK is upregulated in septic shock innate immune cells.
- Sustained MerTK overexpression predicts poor outcomes in septic shock.
- Further investigation into TAM receptors' role in injury-induced immune dysfunction is warranted.
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