The Relationship Between Sepsis-induced Immunosuppression and Serum Toll-like Receptor 9 Level

Abstract

Background/Aim: Our aim was to determine serum TLR-9 levels in sepsis and evaluate the relationship between sepsis and serum TLR-9 levels. Materials and Methods: The study group consisted of 80 consecutive patients with sepsis and 100 healthy individuals. The demographic characteristics, co-morbidities and hemodynamic data of all patients were recorded. Results: TLR-9 serum levels in sepsis were statistically significantly lower compared to the control group. It was also seen that when the lactate level was >5 mmol/l in patients in the sepsis group, the serum TLR-9 levels were substantially higher. Conclusion: There is a relationship between sepsis-induced immunosuppression and serum TLR-9 levels. The host immunity system can be activated by means of TLR-9-related systems, while hyperlactatemia may play a stimulating role in the re-activation of the immune system.Sepsis is a serious clinical problem worldwide (1-3). Severe sepsis and septic shock lead to significant morbidity and mortality in critically-ill patients despite improvements in intensive care and treatment methods (4). Sepsis is characterized by an uncontrolled systemic inflammatory response in the immune system as a result of complex interactions between host and infectious agents (5). Sepsis, serious sepsis, and septic shock represent increasingly severe degrees of systemic inflammatory responses to infection (6). Increased uncontrolled inflammatory response leads to increased mortality from sepsis.Toll-like receptors (TLRs) have been recognized as a component of the innate immune system. TLRs have an important role in the innate immune system to recognize many pathogens and create a host immune response through production of necrosis factor-α, interleukin (IL)-1, IL6 and other pro-inflammatory cytokines (7, 8). In our study, serum TLR9 levels in sepsis were analyzed in relation to clinical and prognostic parameters. Patients and MethodsThis prospective study was approved by the Ethics Committee of the Istanbul University, Turkey (Approval number 1341). All the procedures followed in the study were in accordance with the Declaration of Helsinki. Informed consent was obtained from all individual participants included in the study. A total of 180 patients were enrolled in the study. The study group consisted of 80 consecutive patients with diagnosis of sepsis at the intensive care unit. In each case, diagnoses were established with histological examination. The control group comprised 100 healthy individuals. The demographic characteristics, co-morbidities and hemodynamic data of all patients were recorded. Blood gas samples and laboratory data of the cases were collected. Microbial cultures of blood, sputum, a wound swab, abscess, and urine from each patient were performed. Blood samples were collected in EDTA-coated tubes by standard venipuncture method. The serum samples of the participants were stored at −20˚C until analysis. TLR9 levels were

Macrophage-Derived Exosomes in TLR9-/- Mice Ameliorate Sepsis-Induced Mitochondrial Oxidative Stress and Apoptosis in Cardiomyocytes

“…Macrophage-derived exosomes can participate in innate immune response-induced inflammation through synergistic action with toll-like receptors (TLR) [ 13 ]. TLR are regarded as an integral part of the innate immune system [ 14 ], among which TLR9 can recognize microbial DNA [ 15 ]. Moreover, it has been found that macrophage-derived exosomes can recognize long-chain fatty acids, activate the downstream ERK signaling pathway, and promote the secretion of inflammatory factors [ 16 ] and proinflammatory cytokines such as TNF- α and L-1 β , thus inducing the systemic inflammatory cascade response and causing myocardial injury, apoptosis, and cardiac dysfunction [ 17 ].…”

“…Excessive immune responses are detrimental to the host and negative feedback regulation, and PI3K plays as a primary endogenous suppressor for TLR-induced inflammatory signals in macrophages, which is crucial for the maintenance of immune system as well as cellular structure integrity [18][19][20]. Previously, much studies were focused on the inflammatory responses and TLR9 signals, whereas the relationship between the PI3K signal-induced exosome secretion and TLR9 activation remains unclear and ambiguous [15,21]. Therefore, this study was carried on to elaborate on these mechanisms.…”

Toll-like receptors in sepsis-associated cytokine storm and their endogenous negative regulators as future immunomodulatory targets

“…However, TLR9 (-1486 T > C) and TLR-9 (C > T) gene polymorphisms do not show any correlation with sepsis [67] . The serum TLR9 levels are low in sepsis patients but their circulating levels increases at later immunosuppressive stage of sepsis, including septic shock in patients with a higher (greater than 5 mmol/l) lactate level [68] . This indicates that the profound immune cell death may have caused the increase in the circulating TLR9 (recognizes bacterial and viral DNA).…”

Innate Receptor Activation Patterns Involving TLR and NLR Synergisms in COVID-19, ALI/ARDS and Sepsis Cytokine Storms: A Review and Model Making Novel Predictions and Therapeutic Suggestions

“…RIG1 mRNA was also upregulated in human sepsis patients but not the protein expression [ 101 ]. In sum, all that can be said in general about innate activation in sepsis is that TLR2, TLR4, TLR5, TLR7 and NLRP3 [ 102 ] can be, but are not necessarily, activated, while TLR9 may or may not be downregulated [ 103 , 104 , 105 ]. The same generalizations can be made about murine polymicrobial sepsis models [ 91 , 106 , 107 , 108 ], suggesting that sepsis is not a single, definable disease [ 97 ].…”