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Background: The aim of this study is to investigate the diagnostic value of cerebrospinal fluid (CSF) and serum levels of the soluble form of triggering receptor-1 expressed on myeloid cells (sTREM-1) in neonatal meningitis. Methods: Serum sTREM-1 levels were measured in all neonatal sepsis patients at the start of antibiotic therapy and the 48th hour of treatment. At the beginning of antibiotic therapy, CSF samples were collected for sTREM-1 measurements. Control CSF samples were also collected from the patients with meningitis at the 48th hour of treatment. Results: A total of 77 preterm (50) and term (27) patients with neonatal sepsis were included in the study. There was no significant difference between the CSF sTREM-1 levels of patients with and without meningitis. The CSF sTREM-1 levels of preterm infants with meningitis decreased significantly after treatment (p = 0.038). Although the CSF/serum sTREM-1 ratios tended to increase in babies with meningitis, no significant difference was found between the groups. CSF/serum sTREM-1 ratios (mean ± SD) were 1.42 ± 0.91 and 1.14 ± 0.85 in preterm babies with and without meningitis and 1.15 ± 0.97 and 0.97 ± 0.55 in term babies with and without meningitis, respectively. Conclusions: Serum and CSF sTREM-1 levels increase in patients with neonatal sepsis. CSF s-TREM-1 levels decrease after treatment in preterm infants with meningitis.

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Introduction: Recently, NLR family pyrin domain containing 3 (NLRP3) and pyroptosis have been reported to be involved in traumatic brain injury-induced acute lung injury (TBI-ALI). Studies have shown that triggering receptor expressed on myeloid cells-1 (TREM-1) may be one of the upstream molecules regulating NLRP3/pyroptosis, and 5-hydroxytryptamine type 3-receptor (5-HT3R) antagonists can inhibit NLRP3/pyroptosis. However, the role of TRME-1 in TBI-ALI, the therapeutic effect of 5-HT3R inhibition on TBI-ALI and its mechanism are still unclear. Therefore, this study aimed to evaluate the protective effect of ondansetron, a 5-HT3 inhibitor, on TBI-ALI, and to explore whether the underlying mechanism is related to the regulation of TREM-1. Material and methods: A TBI-ALI rat model was constructed via lateral fluid percussion (LFP) brain injury, and either TREM-1 inhibitor (LP17) or ondansetron was administered as needed. Results: TBI induced NLRP3 inflammasome, pyroptosis, and TREM-1 activation in rat lung tissues in a time-dependent manner. Inhibition of TREM-1 activity attenuated TBI-ALI; this is evident from reduced pathological scores, wet/dry ratios, and bronchoalveolar lavage fluid protein levels and alleviated NLRP3 inflammasome/pyroptosis. In addition, ondansetron reduced NLRP3 inflammasome/pyroptosis and alleviated TBI-ALI. Moreover, ondansetron reduced TREM-1 activation in macrophages and lung tissue. Conclusions: Ondansetron alleviated TBI-ALI. In terms of mechanism, TREM-1 promotes TBI-ALI via the NLRP3-related pyroptosis pathway, and the protective effect of ondansetron on TBI-ALI may be related to the inhibition of TREM-1.

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Purpose: Proper antibiotic administration is crucial for sepsis management. Given the escalating incidence of antimicrobial resistance, there is a pressing need for indicators of antimicrobial susceptibility with short turnaround times. This study aimed to investigate the potential of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as an early biomarker for in vivo antibiotic susceptibility in patients with sepsis. Patients and Methods: We conducted a retrospective analysis of plasma samples from patients enrolled in a pre-established study designed to investigate prognostic biomarkers in patients with sepsis or septic shock. Baseline and 6 h sTREM-1 levels were examined using enzyme-linked immunosorbent assays. The primary outcome of the study was the comparison of percentage changes in sTREM-1 levels at the 6 h relative to baseline with respect to antibiotic susceptibility. Results: Of the 596 patients enrolled in the pre-established study, 29 with a median age of 75.8 and a 28-day mortality rate of 17.2% were included in the present analysis. Among these patients, 24 were classified into the susceptible group, whereas the remaining five were classified into the resistant group. The trend in plasma sTREM-1 levels differed with respect to antibiotic susceptibility. Moreover, percentage change in sTREM-1 levels at the 6 h relative to baseline was significantly higher in the resistant group (P = 0.028). Conclusion: The trend in plasma sTREM-1 levels in patients with sepsis differed with respect to antibiotic susceptibility, with a higher percentage change in patients treated with inappropriate antibiotics. These findings indicate the potential utility of sTREM-1 as an early biomarker of antibiotic susceptibility.

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Tuberculosis remains a threat to public health. The only approved vaccine, Bacillus Calmette-Guérin (BCG), is administered intradermally and provides limited protection, and its effect on innate immunity via the respiratory route has not been fully elucidated. A mouse model with genetically depleted TREM1 and seven-color flow cytometry staining were used to characterize the comprehensive immune response induced by respiratory BCG, through evaluating organ bacterial loads, lung histopathology, and lung immunohistochemistry. During respiratory BCG infection, the murine lungs displayed effective bacterial clearance. Notably, marked differences in neutrophils were observed between thymus and bone marrow cells, characterized by a significant increase in the expression of the triggering receptor expressed on myeloid cells 1 (TREM1). Subsequently, upon depletion of TREM1, a reduction in pulmonary neutrophils was observed, which further exacerbated bacterial loads and resulted in worsened pathology following respiratory BCG infection. In summary, up-regulated expression of TREM1 in rapidly increasing circulating neutrophil by pulmonary BCG is required for an efficient host response to BCG infection, and suggests the important role of TREM1 in neutrophil-related pulmonary bacteria clearance and pathology.

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BACKGROUND: Septic acute lung injury (ALI) is a life-threatening condition commonly occurring in the intensive care unit. Inflammation is considered as the basic pathological response of septic ALI. Triggering receptor expressed on myeloid cells 1 (TREM1) is a member of the immunoglobulin superfamily receptors that regulates the inflammatory response. However, the role of TREM1 in septic ALI has not yet been reported. METHODS: Cell viability was tested using the MTT assay. TdT-mediated dUTP nick end labeling assay and flow cytometry were used for apoptosis. The level of protein was detected using western blot analysis. The levels of tumor necrosis factor-α and interleukin-1ß were assessed using enzyme-linked immunosorbent assay. The lactate dehydrogenase content was assessed using the assay kit. Myeloperoxidase activity was determined using an assay. Histology of lung tissue was further analyzed through hematoxylin-eosin staining. RESULTS: We found that TREM1 knockdown by transfection with si-TREM1 inhibited lipopolysaccharide (LPS)-induced cell apoptosis of alveolar macrophage cell line MH-S. The LPS stimulation caused M1 polarization of MH-S cells, which could be reversed by TREM1 knockdown. In vivo assays proved that si-TREM1 injection improved lung injury and inflammation of cecal ligation and puncture-induced ALI in mice. In addition, TREM1 knockdown suppressed the activation of toll-like receptor 4/nuclear factor-kappa B signaling, implying the involvement of TLR4 in the effects of TREM1 in response to LPS stimulation. CONCLUSIONS: This study examined the proinflammatory role of TREM1 in septic ALI and its regulatory effect on alveolar macrophage polarization. These results suggest that TREM1 could potentially serve as a therapeutic target in the prevention and treatment of ALI.

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Objective To investigate the predictive value of serum matrix metalloproteinase-9(MMP-9)and soluble triggering receptor expressed on myeloid cells-1(sTREM-1)in postoperative urinary tract infec-tion(UTI)in patients with ureteral calculi.Methods Among the ureteral calculi patients admitted to the De-partment of Urology in a hospital from October 2021 to October 2022,68 patients with postoperative UTI(UTI group)and 68 patients without UTI(non-UTI group)were selected as the study objects.Serum MMP-9 and sTREM-1 levels were detected by enzyme-linked immunosorbent assay(ELISA).Spearman method was used to analyze the correlation between serum MMP-9 and sTREM-1 levels and clinical data in UTI group,and the predictive value of serum MMP-9 and sTREM-1 levels in postoperative UTI in ureteral calculi patients was analyzed by receiver operating characteristic curve.The influencing factors of postoperative UTI in ureter-al calculi patients were analyzed by multivariate Logistic regression.Results Compared with non-UTI group,serum MMP-9 and sTREM-1 levels in UTI group were significantly increased,with statistical significance(P＜0.05).Correlation analysis showed that serum MMP-9 and sTREM-1 levels were positively correlated in UTI group(r=0.585,P＜0.001).The combined prediction of the area under the curve(AUC)for postopera-tive UTI in ureteral calculi patients was 0.961(95％CI:0.934-0.988).The sensitivity and specificity were 73.36％and 85.68％,respectively.The AUC predicted by MMP-9 and sTREM-1 was higher than that predic-ted by MMP-9 and STREM-1 alone(Z=25.420,P＜0.001;Z=21.531,P＜0.001).The levels of MMP-9 and sTREM-1 were the influencing factors of postoperative UTI in ureteral calculi patients(P＜0.05).Conclusion The serum levels of MMP-9 and sTREM-1 in postoperative UTI in ureteral calculi patients are increased,and the detec-tion of both levels has important predictive value for the occurrence of postoperative UTI in ureteral calculi patients.

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Objective To investigate the role of triggering receptor expressed on myeloid cells-1(TREM-1)in ath-erosclerosis induced by chronic intermittent hypoxia(CIH).Methods ApoE-/-mice were randomly divided into blank group,model group and experimental group.The mice in the model group and the experimental group were kept in a hypoxic environment and fed with a high-fat diet.After 4 weeks of high-fat feeding,mice in the experi-mental group were intraperitoneally injected with TREM-1 inhibitor LR12(5 mg/kg)for 8 weeks.After 12 weeks of feeding,the level of serum total cholesterol(TC),low density lipoprotein(LDL),triglyceride(TG),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-10(IL-10)were detected.Histological analysis of aortic TREM-1 expression,plaque area and macrophage level were examined.Results Compared with blank group,the expression of TREM-1 in the aorta of the model group significantly increased(P＜0.05).Com-pared with model group,the aortic plaque,the level of lipids in serum(TC,LDL,TG)and inflammatory factors(TNF-α,IL-1β,IL-10),aortic plaque,the expression of TREM-1 and infiltrating macrophages in aortic plaque of the experimental group were all significantly reduced(P＜0.05).Conclusions TREM-1 is involved in the develop-ment of CIH-induced AS.Inhibition of TREM-1 can alleviate CIH-induced AS and its mechanism is related to the inhibition of macrophage activation.

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The diagnosis of sepsis still lacks a practical and reliable gold standard. The purpose of this study was to confirm the effect of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) combined with soluble suppression of tumorigenicity 2 (sST2) in the diagnosis of sepsis through the correlation between sTREM-1, sST2, and sequential organ failure assessment (SOFA) scores. Baseline data of 91 patients with sepsis in the intensive care unit were collected, sTREM-1 and sST2 were detected, and the correlation between markers and SOFA score was analyzed. Besides, the prognostic value of baseline and postadmission indicators for sepsis was analyzed with death as the outcome. The results showed that the expressions of sST2 and sTREM-1 in death group and survival group were higher than those in the survival group (p < 0.05). Correlation analysis showed that sST2, sTREM-1, and the joint diagnosis model had a high correlation with SOFA score (p < 0.05), but poor correlation with Acute Physiology and Chronic Health Evaluation Ⅱ score (p > 0.05). Among them, joint diagnosis model has the highest correlation. Receiver operating characteristic curve analysis showed that combined diagnosis had higher area under curve values. sTREM-1/sST2 can be better used in the diagnosis of sepsis than the single biomarker detection, and the combination of the above two biomarkers has potential application value in the detection and prognosis prediction of sepsis.

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BACKGROUND: Intracerebral hemorrhage (ICH) is a high mortality and disability stroke subtype. Destruction of the blood-brain barrier (BBB) is a crucial contributor to brain edema and neurological deficit after ICH. Triggering receptor expressed on myeloid cells 1 (TREM-1) has been reported to be expressed in endothelial cells, but its role in ICH remains unclear. This study aims to evaluate the role of TREM-1 on BBB permeability after ICH in mice. METHODS: Two hundred and forty-two CD1 mice were used in this study. The ICH model was established by collagenase injection. LP17 was administered intranasally at 2 or 8 h after ICH to inhibit TREM-1. To explore the underlying mechanism, SYK activation CRISPR was administered intracerebroventricularly with LP17, and Anti-mouse TREM-1 rat IgG2a (a specific TREM-1 agonist) was injected intracerebroventricularly with R406 (a specific SYK inhibitor) intraperitoneally. Neurobehavioral outcome, brain water content, BBB permeability, and protein expression were evaluated. RESULTS: The expression level of the TREM-1 receptor increased rapidly as early as 6 h after ICH, and it was mainly expressed on the endotheliocytes in the neurovascular unit. Early and delayed administration of LP17 significantly decreased brain edema and improved neurobehavioral outcomes at 24 h after ICH. LP17 reduced the BBB permeability by increasing ß-catenin, claudin-5 and ZO-1 expression. Furthermore, SYK activation CRISPR abolished the beneficial effect of LP17 on the expression of the above junction molecules. Meanwhile, R406 reversed the impact of the TREM-1 activator on the downregulation of ß-catenin, claudin-5 and ZO-1 expression. CONCLUSIONS: This study demonstrated that TREM-1 deteriorated BBB permeability via modulating the expression of interendothelial junction molecules after ICH, and this regulation is partly mediated by the SYK/ß-catenin signaling pathway.

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Fibrosing pneumonia (FP) is classified into usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP), each having its own etiology and prognosis. Both types of FP are progressive and chronic conditions with distinct etiologies. Cytokines and inflammatory mediators play critical roles in the pathogenesis of FP. Among them, the role of transforming growth factor beta-1 (TGF-ß1) and modulators triggering fibrosis are not well understood. In this study, the expression of triggering receptor expressed on myeloid cells-1 (TREM-1) as a stimulator for the production of TGF-ß1 and also CD4+CD25+Foxp3+ regulatory cells were investigted in FP patients. Sixteen UIP, 14 NSIP and 4 pulmonary fibrosis following Mycobacterium tuberculosis (TB) infection patients, were compared with 12 healthy controls. The frequency of blood CD14+TGF-ß1+ and CD14+TREM1+-gated monocytes and CD4+CD25+Foxp3+ regulatory T cells (Treg), as well as the plasma levels of TGF-ß1 and IL­10 were measured. Fibrosis patients compared to healthy controls had a greater frequency of CD14+TGF-ß1+ [15.9 (0.2-88.2) vs. 0.6 (0.2-11.0)] and CD14+TREM1+ [21.1 (2.3-91.2) vs. 10.3 (3.1-28.6)]-gated monocytes, and CD4+CD25+Foxp3+ [1.2 (0.3-3.6) vs. 0.2 (0.1-0.4)]-gated lymphocytes. Plasma TGF-ß1 were also significantly increased in patients with fibrosis compared to healthy controls [9316.2 (±5554.4) vs. 3787.5 (±2255.6)]. These results confirm the importance of TGF-ß1 and TREM1 in pulmonary fibrosis. It seems that this reciprocal cycle in healthy people is modulated by the production of IL­10 by Treg cells, thus limiting fibrosis, as observed in patients following TB infection. Further investigations are recommended to evaluate possible immunomodulatory mechanisms defects in pulmonary fibrosis.

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Sepsis-acquired immunosuppression may play a major role in patients' prognosis through increased risk of secondary infections. Triggering receptor expressed on myeloid cells 1 (TREM-1) is an innate immune receptor involved in cellular activation. Its soluble form (sTREM-1) has been described as a robust marker of mortality in sepsis. The objective of this study was to evaluate its association with the occurrence of nosocomial infections alone or in combination with human leucocyte antigen-DR on monocytes (mHLA-DR). DESIGN: Observational study. SETTING: University Hospital in France. PATIENTS: One hundred sixteen adult septic shock patients as a post hoc study from the IMMUNOSEPSIS cohort (NCT04067674). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma sTREM-1 and monocyte HLA-DR were measured at day 1 or 2 (D1/D2), D3/D4, and D6/D8 after admission. Associations with nosocomial infection were evaluated through multivariable analyses. At D6/D8, both markers were combined, and association with increased risk of nosocomial infection was evaluated in the subgroup of patients with most deregulated markers in a multivariable analysis with death as a competing risk. Significantly decreased mHLA-DR at D6/D8 and increased sTREM-1 concentrations were measured at all time points in nonsurvivors compared with survivors. Decreased mHLA-DR at D6/D8 was significantly associated with increased risk of secondary infections after adjustment for clinical parameters with a subdistribution hazard ratio of 3.61 (95% CI, 1.39-9.34; p = 0.008). At D6/D8, patients with persistently high sTREM-1 and decreased mHLA-DR presented with a significantly increased risk of infection (60%) compared with other patients (15.7%). This association remained significant in the multivariable model (subdistribution hazard ratio [95% CI], 4.65 [1.98-10.9]; p < 0.001). CONCLUSIONS: In addition to its prognostic interest on mortality, sTREM-1, when combined with mHLA-DR, may help to better identify immunosuppressed patients at risk of nosocomial infections.

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The exacerbation of the inflammatory response caused by SARS-CoV-2 in adults promotes the production of soluble mediators that could act as diagnostic and prognostic biomarkers for COVID-19. Among the potential biomarkers, the soluble triggering receptor expressed on myeloid cell-1 (sTREM-1) has been described as a predictor of inflammation severity. The aim was to evaluate sTREM-1 and cytokine serum concentrations in pediatric patients during the acute and convalescent phases of COVID-19. This was a prospective study that included 53 children/adolescents with acute COVID-19 (Acute-CoV group); 54 who recovered from COVID-19 (Post-CoV group) and 54 controls (Control group). Preexisting chronic conditions were present in the three groups, which were defined as follows: immunological diseases, neurological disorders, and renal and hepatic failures. The three groups were matched by age, sex, and similar preexisting chronic conditions. No differences in sTREM-1 levels were detected among the groups or when the groups were separately analyzed by preexisting chronic conditions. However, sTREM-1 analysis in the seven multisystemic inflammatory syndrome children (MIS-C) within the Acute-Cov group showed that sTREM-1 concentrations were higher in MIS-C vs non-MIS-C acute patients. Then, the receiver operating curve analysis (ROC) performed with MIS-C acute patients revealed a significant AUC of 0.870, and the sTREM-1 cutoff value of > 5781 pg/mL yielded a sensitivity of 71.4 % and a specificity of 91.3 % for disease severity, and patients with sTREM-1 levels above this cutoff presented an elevated risk for MIS-C development in 22.85-fold (OR = 22.85 [95 % CI 1.64-317.5], p = 0.02). The cytokine analyses in the acute phase revealed that IL-6, IL-8, and IL-10 concentrations were elevated regardless of whether the patient developed MIS-C, and those levels decreased in the convalescent phase, even when compared with controls. Spearman correlation analysis generated positive indexes between sTREM-1 and IL-12 and TNF-α concentrations, only within the Acute-CoV group. Our findings revealed that sTREM-1 in pediatric patients has good predictive accuracy as an early screening tool for surveillance of MIS-C cases, even in patients with chronic underlying conditions.

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According to the linear model of microarray data analysis, triggering receptor expressed on myeloid cells 1 (TREM1) has been shown to have a significantly different expression profile between intervertebral disc degeneration (IDD) samples and associated control samples. The purpose of the present study was to explore the probable role and underlying mechanism of TREM1 in IDD. To accomplish this, an in vitro model of IDD was established by using IL-1ß to stimulate human nucleus pulposus cells (NPCs). After the level of TREM1 had been determined, its functions in terms of the viability of the NPCs, extracellular matrix (ECM) degradation, inflammation, apoptosis and endoplasmic reticulum stress (ERS) were assessed. The downstream target of TREM1 was predicted to be Toll-like receptor-4 (TLR-4) and its roles were then studied, incorporating experiments featuring an ERS agonist. IL-1ß was found to elevate the level of TREM1 in NPCs. TREM1 knockdown reversed the observed effects of IL-1ß on cell viability, ECM degradation, inflammation, apoptosis of NPCs, ERS and TLR4/NF-κB signaling. Subsequently, the TLR4 and ERS agonists were found to reverse the effect of TREM1 knockdown on NPCs, indicating that the TLR4/NF-κB signaling pathway and ERS were responsible for mediating the regulation of TREM1. In conclusion, the present study showed that TREM1 knockdown blocked the TLR4/NF-κB signaling pathway, inhibited ERS and reduced the levels of ECM degradation and apoptosis of NPCs induced by IL-1ß.

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Proper selection of susceptible antibiotics in drug-resistant bacteria is critical to treat bloodstream infection. Although biomarkers that guide antibiotic therapy have been extensively evaluated, little is known about host biomarkers targeting in vivo antibiotic susceptibility. Therefore, we aimed to evaluate the trends of hemodynamics and biomarkers in a porcine bacteremia model treated with insusceptible antibiotics compared to those in susceptible models. Extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (E. coli, 5.0 * 10^9 CFU) was intravenously administered to 11 male pigs. One hour after bacterial infusion, pigs were assigned to two groups of antibiotics, ceftriaxone (n = 6) or ertapenem (n = 5). Pigs were monitored up to 7 h after bacterial injection with fluid and vasopressor support to maintain the mean arterial blood pressure over 65 mmHg. Blood sampling for blood culture and plasma acquisition was performed before and every predefined hour after E. coli injection. Cytokine (tumor necrosis factor-α, interleukin [IL]-1ß, IL-6, IL-8, IL-10, C-reactive protein, procalcitonin, presepsin, heparan sulfate, syndecan, and soluble triggering receptor expressed on myeloid cells-1 [sTREM-1]) levels in plasma were analyzed using enzyme-linked immunosorbent assays. Bacteremia developed after intravenous injection of E. coli, and negative conversion was confirmed only in the ertapenem group. While trends of other biomarkers failed to show differences, the trend of sTREM-1 was significantly different between the two groups (P = 0.0001, two-way repeated measures analysis of variance). Among hemodynamics and biomarkers, the sTREM-1 level at post 2 h after antibiotics administration represented a significant difference depending on susceptibility, which can be suggested as a biomarker candidate of in vivo antibiotics susceptibility. Further clinical studies are warranted for validation. IMPORTANCE Early and appropriate antibiotic treatment is a keystone in treating patients with sepsis. Despite its importance, blood culture which requires a few days remains as a pillar of diagnostic method for microorganisms and their antibiotic susceptibility. Whether changes in biomarkers and hemodynamics indicate treatment response of susceptible antibiotic compared to resistant one is not well understood to date. In this study using extended-spectrum ß-lactamase -producing E. coli bacteremia porcine model, we have demonstrated the comprehensive cardiovascular hemodynamics and trends of plasma biomarkers in sepsis and compared them between two groups with susceptible and resistant antibiotics. While other hemodynamics and biomarkers have failed to differ, we have identified that levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) significantly differed between the two groups over time. Based on the data in this study, trends of sTREM-1 obtained before the antibiotics and 2~4 h after the antibiotics could be a novel host biomarker that triggers the step-up choice of antibiotics.

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OBJECTIVE: The objective of this was to study the relationship between vitamin D receptor (VDR) and triggering receptor expressed on myeloid cells 1 (TREM-1) gene single-nucleotide polymorphisms (SNP) and neonatal sepsis susceptibility and prognosis. METHODS: The blood of 150 neonatal sepsis patients and 150 normal neonates was collected, and genomic DNA was extracted. Sanger sequencing was used to analyze the genotypes of VDR rs739837 and TREM-1 rs2234246. RESULTS: Vitamin D receptor rs739837 locus GT, TT genotype, dominant model, and recessive model were all protective factors for sepsis (0 < OR < 1, p < 0.05). The risk of sepsis in carriers of the rs739837 G allele was 0.65 times that of the rs739837 T allele (95% CI: 0.50-0.83, p < 0.001), CT, TT, dominant model, and recessive model at rs2234246 were risk factors for sepsis (OR > 1, p < 0.05). The risk of sepsis in carriers of the rs739837 T allele was 1.38 times that of carriers of the C allele (95% CI: 1.16-1.61, p < 0.001). The polymorphisms of VDR gene rs739837 and TREM-1 gene rs2234246 were not significantly correlated with the survival of patients with neonatal sepsis (p > 0.05). CONCLUSION: Vitamin D receptor gene rs739837 locus G>T is associated with a reduction in the risk of neonatal sepsis, TREM-1 rs2234246 C>T is associated with the increased risk of neonatal sepsis, but none of them was significantly associated with the prognosis of neonatal sepsis.

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BACKGROUND AND OBJECTIVES: The aim of this study is to investigate the effect of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in idiopathic granulomatous mastitis (IGM). METHODS: This case-control study was conducted in Saglik Bilimleri and Necmettin Erbakan Universities. Sixty patients with IGM diagnosis (Group P) and 25 healthy females as control group (Group C) were included. Group P was divided into two subgroups according to the activity of disease: patients with active lesion (Group PA), and patients without any symptoms, in remission (Group PR). The ELISA method was used to measure sTREM-1 level. RESULTS: Group P's sTREM-1 were higher than Group C (p < .0001). The difference between sTREM-1 levels of Groups PA, PR and C was significant statistically (p < .0001). Group PA's sTREM-1 levels were higher than Group C (p < .0001). Also, sTREM-1 levels of Group PR were higher than Group C (p = .006). When sTREM-1 levels of patients receiving steroid therapy and did not in Group PR were analyzed, the sTREM-1 levels of the patients not receiving steroid treatment were found to be statistically higher than Group C (p = .002). Although the sTREM-1 levels of the patients who did not receive steroid therapy were higher than those who received steroid therapy, the difference was not statistically significant (p > .05). CONCLUSION: We concluded that the detected high sTREM-1 levels contributed to inflammation in IGM. In particular, blockade of TREM may be a promising treatment option in resistant or multiple recurrent patients.

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BACKGROUND: Efficient and accurate diagnosis of neonatal sepsis is challenging. The potential impact for a reduction in morbidity and mortality as well as antibiotic usage has stimulated the ongoing search for biomarkers of early sepsis. The objective of this pilot study was to quantify the levels of sTREM-1 and correlate with blood cultures and inflammatory markers in neonates evaluated for sepsis. METHODS: Neonates with suspected sepsis were enrolled (n = 83; Preterm n = 35; Term n = 48). Routine bloods for sepsis evaluation were included and plasma sTREM-1 levels were quantified by ELISA. RESULTS: Term and preterm neonates (n = 83; Preterm n = 35; Term n = 48) were enrolled and 16 neonates had positive blood cultures (preterm n = 15; term n = 1). sTREM-1 levels were not significantly different in infants with culture-positive or culture-negative sepsis (356 ± 218 pg/mL and 385 ± 254 pg/mL respectively). The immature-to-total granulocyte (I/T) ratio showed a significant positive correlation with sTREM-1 in the preterm group with positive blood cultures. Additionally, sTREM-1 showed a positive correlation with CRP in the preterm group with negative blood cultures. CONCLUSIONS: sTREM-1 was associated with traditional markers of inflammation (I/T ratio and CRP). However, in this cohort sTREM-1 did not improve the early detection of neonatal culture-positive sepsis.

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Triggering receptor expressed on myeloid cells-1 (TREM-1) exists in two forms: a transmembrane form and a soluble form (sTREM-1). The levels of sTREM-1 are elevated in supernatants of activated HSCs. However, the role of sTREM-1 in HSC activation and liver fibrosis remains undefined. Previous studies have primarily focused on the transmembrane form of TREM-1; we innovatively observed the function of sTREM-1 as a ligand in liver fibrosis and screened its receptor. Here, recombinant sTREM-1 was used as a stimulator which induced HSC activation and further aggravated liver fibrosis. Then, screening for sTREM-1 interacting membrane receptors was performed using pull-down assay followed by mass spectrometry, and the membrane receptor roundabout guidance receptor 2 (Robo2) was identified as a candidate receptor for sTREM-1. The interaction between sTREM-1 and Robo2 was verified by pull-down and immunofluorescence. The role of Robo2 on sTREM-1-induced HSC activation and its downstream signal pathways was assessed by knockdown of Robo2 in LX-2 cells. Furthermore, HSC-specific knockdown of Robo2 was achieved in a mouse model of liver fibrosis by using a recombinant adeno-associated virus (AAV) vector to confirm the role of the receptor, and we proved that Robo2 knockdown inhibited the activation of HSC and liver fibrosis, which also led to the inactivation of Smad2/3 and PI3K/Akt pathways in sTREM-1-induced HSC activation and liver fibrosis. In conclusion, sTREM-1 acts as a new ligand of Robo2; the binding of sTREM-1 to Robo2 initiates the activation of the downstream Smad2/3 and PI3K/Akt signalling pathways, thereby promoting HSC activation and liver fibrosis.

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BACKGROUND: Triggering receptor expressed on myeloid cells-1 (TREM-1) participates in neuroinflammation. We intended to ascertain whether serum soluble TREM-1 (sTREM-1) could be utilized as a biomarker of inflammation, severity, early neurologic deterioration (END) and outcome after primary intracerebral hemorrhage (ICH). METHODS: Serum sTREM-1 levels were gauged in 104 ICH patients and 104 healthy controls. END was diagnosed when the National Institutes of Health Stroke Scale (NIHSS) score increased ≥ 4 points or death between admission and 24 h after admission. Patients with a modified Rankin scale score of > 2 at 3 months were considered to have poor outcome. RESULTS: As compared to controls, patients exhibited significantly elevated serum sTREM-1 levels (median: 309.0 vs 67.9 pg/ml). Serum sTREM-1 concentrations were intimately correlated with NIHSS score (r = 0.574), hematoma volume (r = 0.554), blood leukocyte count (r = 0.529) and serum C-reactive protein concentrations (r = 0.509). Serum sTREM-1 concentrations > 309.0 pg/ml independently predicted END and poor outcome with odds ratio values of 4.054 and 4.721 respectively. Serum sTREM-1 concentrations distinguished END and poor outcome with areas under receiver operating characteristic curve of 0.789 and 0.813 respectively. CONCLUSION: Serum sTREM-1 may represent a promising inflammatory biomarker for assessment of severity and prediction of END and poor outcome after ICH.

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