Impaired Surface Expression of HLA-DR, TLR2, TLR4, and TLR9 in Ex Vivo-In Vitro Stimulated Monocytes from Severely Injured Trauma Patients

Heftrig, David; Sturm, Ramona; Oppermann, Elsie; Kontradowitz, Kerstin; Jurida, Katrin; Schimunek, Lukas; Woschek, Mathias; Marzi, Ingo; Relja, Borna

doi:10.1155/2017/2608349

Cited by 15 publications

(17 citation statements)

References 66 publications

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“…(2017) reported different results for the circulating levels of monocytes, while a constant depression of MHC-II expression as well as an impaired production of IL-1β over the time course of ten days after trauma compared to healthy volunteers was observed. [ 10 ]…”

Section: Introductionmentioning

confidence: 99%

“…[ 23 ] Other studies have shown an impaired expression of TLR2 in trauma patients during the first 48 hours or over a time course of 10 days after trauma compared to healthy volunteers. [ 10 , 24 ]…”

Section: Introductionmentioning

confidence: 99%

“…[ 27 , 28 ] With regard to trauma, a decreased MHC-II expression in human monocytes after trauma has been reported. [ 10 , 29 ] Nonetheless, the expression profile of H(S)LAs, the porcine MHC molecules, still remains not fully discovered, and even less is known about their behavior after trauma. MHC-I and MHC-II molecules were first observed on monocytes in pigs by Chamorro et al .…”

Section: Introductionmentioning

confidence: 99%

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Early decreased TLR2 expression on monocytes is associated with their reduced phagocytic activity and impaired maturation in a porcine polytrauma model

et al. 2017

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In their post-traumatic course, trauma patients suffering from multiple injuries have a high risk for immune dysregulation, which may contribute to post-injury complications and late mortality. Monocytes as specific effector cells of the innate immunity play a crucial role in inflammation. Using their Pattern Recognition Receptors (PRRs), notably Toll-Like Receptors (TLR), the monocytes recognize pathogens and/or pathogen-associated molecular patterns (PAMPs) and organize their clearance. TLR2 is the major receptor for particles of gram-positive bacteria, and initiates their phagocytosis. Here, we investigated the phagocytizing capability of monocytes in a long-term porcine severe trauma model (polytrauma, PT) with regard to their TLR2 expression. Polytrauma consisted of femur fracture, unilateral lung contusion, liver laceration, hemorrhagic shock with subsequent resuscitation and surgical fracture fixation. After induction of PT, peripheral blood was withdrawn before (-1 h) and directly after trauma (0 h), as well as 3.5 h, 5.5 h, 24 h and 72 h later. CD14+ monocytes were identified and the expression levels of H(S)LA-DR and TLR2 were investigated by flow cytometry. Additionally, the phagocytizing activity of monocytes by applying S. aureus particles labelled with pHrodo fluorescent reagent was also assessed by flow cytometry. Furthermore, blood samples from 10 healthy pigs were exposed to a TLR2-neutralizing antibody and subsequently to S. aureus particles. Using flow cytometry, phagocytizing activity was determined. P below 0.05 was considered significant. The number of CD14+ monocytes of all circulating leukocytes remained constant during the observational time period, while the percentage of CD14+H(S)LA-DR+ monocytes significantly decreased directly, 3.5 h and 5.5 h after trauma. The percentage of TLR2+ expressing cells out of all monocytes significantly decreased directly, 3.5 h and 5.5 h after trauma. The percentage of phagocytizing monocytes decreased immediately and remained lower during the first 3.5 h after trauma, but increased after 24 h. Antagonizing TLR2 significantly decreased the phagocytizing activity of monocytes. Both, decreased percentage of activated as well as TLR2 expressing monocytes persisted as long as the reduced phagocytosis was observed. Moreover, neutralizing TLR2 led to a reduced capability of phagocytosis as well. Therefore, we assume that reduced TLR2 expression may be responsible for the decreased phagocytizing capacity of circulating monocytes in the early post-traumatic phase.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Early decreased TLR2 expression on monocytes is associated with their reduced phagocytic activity and impaired maturation in a porcine polytrauma model

et al. 2017

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“…Previously, we showed that the ex vivo ability of these trauma patients to generate an immune response to lipopolysaccharide stimulation was impaired when compared with healthy volunteers 34. Also, trauma patients have lower expressions of monocyte toll-like receptors compared to healthy volunteers 35. Furthermore, underlining these results, a study performed in 166 polytrauma patients revealed a similar pattern of early IL-10 release and a decrease in human leukocyte antigen—DR isotype expression, potentially reducing macrophage functions 36.…”

Section: Discussionmentioning

confidence: 83%

Early increase in anti-inflammatory biomarkers is associated with the development of multiple organ dysfunction syndrome in severely injured trauma patients

Kleinveld

Boer

Hollmann

et al. 2019

Trauma Surg Acute Care Open

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BackgroundAs a result of improvements in the early resuscitation phase of trauma, mortality is largely driven by later mortality due to multiple organ dysfunction syndrome (MODS), which may be mediated by an early overdrive in the host immune response. If patients at risk for MODS could be identified early, preventive treatment measures could be taken. The aim of this study is to investigate whether specific biomarkers are associated with MODS.MethodsMultiple trauma patients presenting to the Amsterdam University Medical Centers, location Academic Medical Center, between 2012 and 2018 with an Injury Severity Score of 16 or higher were sampled on arrival at the emergency department. A wide variety of inflammatory cytokines, endothelial and lung-specific markers were determined. Comparisons were made between patients with and without MODS. Univariate and multivariate logistic regression was used to determine associations between specific biomarkers and MODS. A p value of 0.05 was considered to be statistically significant.ResultsIn total, 147 multiple trauma patients were included. Of these, 32 patients developed MODS (21.7%). Patients who developed MODS were more severely injured, had more traumatic brain injury and showed more deranged markers of coagulation when compared with patients without MODS. Overall, both proinflammatory and anti-inflammatory cytokines were higher in patients with MODS, indicative of a host immune reaction. In the multivariate analysis, the combination of anti-inflammatory proteins interleukin 1 receptor antagonist (IL-1RA) (OR 1.27 (1.07–1.51), p=0.002) and Clara cell protein 16 (CC-16) (1.06 (1.01–1.05), p=0.031) was most strongly associated with the development MODS.ConclusionsIn trauma, anti-inflammatory proteins IL-1RA and CC-16 have the potential to early identify patients at risk for development of MODS. Further research is warranted to prospectively validate these results.Level of evidencePrognostic study, level III.

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“…We speculate that TLR2 and TLR4 have the same signal (MyD88-dependent) pathway in new-onset atrial fibrillation patients after acute myocardial infarction. 28,29) As past studies have indicated, new-onset AF after MI is most dependent on infarction size, and AF also could cause harmful cardiovascular events and high mortality. A blood sample is collected before reperfusion therapy and patients only received aspirin, plavix, and statins.…”

Section: Discussionmentioning

confidence: 99%

Toll-Like Receptors 2 and 4 Predict New-Onset Atrial Fibrillation in Acute Myocardial Infarction Patients

Zhang

Shao

2018

Int. Heart J.

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SummaryMyocardial infarction (MI) can cause new-onset atrial fibrillation (AF) due to cardiac remodeling. As a recent study has shown, inflammatory factors are closely tied to cell death and survival in myocardial ischemia injury. Toll-like receptors (TLRs) have been shown to participate in the process of myocardial infarction as innate immune factors.The subjects were divided into 3 groups: healthy controls (n = 82), MI patients (n = 84), and AFMI (newonset atrial fibrillation after myocardial infarction) patients (n = 85). Peripheral blood mononuclear cell (PBMC) TLR mRNA expression was detected by rt-PCR. Western blot was used to analyze PBMC TLRs and their downstream signal protein expression. PBMCs were presented as TLR2 expression or TLR4 expression using flow cytometry.From mRNA to protein detection, PBMC TLR2 and TLR4 were significantly higher in the AFMI group than in the control group and MI group. A similar tendency was also observed in the expression of downstream signaling proteins. When further analyzed with TLR2 and TLR4 antibodies by flow cytometry, PBMC levels also appeared to be higher in AFMI patients than those in MI patients and the healthy control group.In our study, PBMC TLRs and their downstream signaling proteins were significantly higher in the acute myocardial infarction patients with new-onset atrial fibrillation compared with healthy people and acute myocardial infarction patients without new-onset atrial fibrillation. They have the potential to be novel biomarkers for new-onset atrial fibrillation after acute myocardial infarction.(Int Heart J 2018; 59: 64-70) Key words: Innate immune A s one component of the global burden of cardiac arrhythmia disease, atrial fibrillation (AF) is generally divided into valvular and non-valvular AF. Myocardial infarction (MI) is an independent risk factor for new-onset AF which occurs in 6% to 21% of acute MI patients due to post myocardial infarction remodeling. [1][2][3][4][5] Unfortunately, AF is highly associated with substantial morbidity and mortality increases after myocardial infarction. 6-8) Editorial p.3Innate immune factors play important roles in most cardiac diseases. [9][10][11] As data has shown in recent research, toll-like receptors increase in either plasma or tissues as innate immune factors in ischemia heart diseases and arrhythmias diseases. [12][13][14] Notably, TLR4 could directly stimulate macrophages and induce atheroma formation, while TLR4 deficiency has been shown to have a protective effect against myocardial ischemic injury. 15,16) Furthermore, there is some evidence for TLR4 in ventricular remodeling after acute myocardial infarction. 17,18) However, the effect of TLR2 on heart disease remains controversial. In TLR2 knock-out mice, there was no obvious difference in infarct size compared to wild type mice, although a negative effect on fibrosis in the non-infarcted area and a positive effect on left ventricular remodeling have been reported. 19,20) However, TLR2 also has been found to trigger atrial fibrillation and fa...

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Impaired Surface Expression of HLA-DR, TLR2, TLR4, and TLR9 in Ex Vivo-In Vitro Stimulated Monocytes from Severely Injured Trauma Patients

Cited by 15 publications

References 66 publications

Early decreased TLR2 expression on monocytes is associated with their reduced phagocytic activity and impaired maturation in a porcine polytrauma model

Early decreased TLR2 expression on monocytes is associated with their reduced phagocytic activity and impaired maturation in a porcine polytrauma model

Early increase in anti-inflammatory biomarkers is associated with the development of multiple organ dysfunction syndrome in severely injured trauma patients

Toll-Like Receptors 2 and 4 Predict New-Onset Atrial Fibrillation in Acute Myocardial Infarction Patients

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