TLRs1-10 Protein Expression in Circulating Human White Blood Cells during Bacterial and COVID-19 Infections

Autor: Chomel, Louise, Vogt, Mathieu, Demiselle, Julien, Le Borgne, Pierrick, Tschirhart, Marine, Morandeau, Valentin, Merdji, Hamid, Miguet, Laurent, Helms, Julie, Meziani, Ferhat, Mauvieux, Laurent
Zdroj: Journal of Innate Immunity; December 2023, Vol. 16 Issue: 1 p216-225, 10p
Abstrakt: Introduction:Toll-like receptors play crucial roles in the sepsis-induced systemic inflammatory response. Septic shock mortality correlates with overexpression of neutrophilic TLR2 and TLR9, while the role of TLR4 overexpression remains a debate. In addition, TLRs are involved in the pathogenesis of viral infections such as COVID-19, where the single-stranded RNA of SARS-CoV-2 is recognized by TLR7 and TLR8, and the spike protein activates TLR4. Methods:In this study, we conducted a comprehensive analysis of TLRs 1–10 expressions in white blood cells from 71 patients with bacterial and viral infections. Patients were divided into 4 groups based on disease type and severity (sepsis, septic shock, moderate, and severe COVID-19) and compared to 7 healthy volunteers. Results:We observed a significant reduction in the expression of TLR4 and its co-receptor CD14 in septic shock neutrophils compared to the control group (p< 0.001). Severe COVID-19 patients exhibited a significant increase in TLR3 and TLR7 levels in neutrophils compared to controls (p< 0.05). Septic shock patients also showed a similar increase in TLR7 in neutrophils along with elevated intermediate monocytes (CD14+CD16+) compared to the control group (p< 0.005 and p< 0.001, respectively). However, TLR expression remained unchanged in lymphocytes. Conclusion:This study provides further insights into the mechanisms of TLR activation in various infectious conditions. Additional analysis is needed to assess their correlation with patient outcome and to evaluate the impact of TLR-pathway modulation during septic shock and severe COVID-19. Toll-like receptors (TLRs) play a crucial role in severe infections. Overexpression of certain TLRs on neutrophils has been associated with increased mortality in patients with infection-induced shock, although the role of TLR4 overexpression is still debated. In addition, TLR7 and TLR8 recognize the SARS-CoV-2 virus, while the spike protein activates TLR4. In this study, we conducted a comprehensive analysis of TLR expression in white blood cells from patients with bacterial and viral infections. 71 patients were included, divided into 4 groups based on infection severity (sepsis, septic shock, moderate, and severe COVID-19), along with 7 control subjects. Notably, we observed a significant reduction in the expression of TLR4 and its co-receptor CD14 in neutrophils of patients with shock compared to controls. Furthermore, severe COVID-19 patients exhibited a significant increase in TLR3 and TLR7 levels in neutrophils compared to the control group. Patients with shock also showed a similar increase in TLR7 expression in neutrophils, along with elevated intermediate monocytes compared to controls. However, TLR expression remained unchanged in lymphocytes. This study provided further insights into the mechanisms of TLR activation in various severe forms of infection. Additional analysis is required to assess their correlation with patient outcomes and evaluate the potential impact of TLR-related therapy on neutrophil activation.
Databáze: Supplemental Index
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