Tuberculosis remains a global health problem caused by infection with Mycobacterium tuberculosis. Numerous studies have established a close correlation between the development of tuberculosis and the roles of neutrophils. Recently, a distinct population of CD15+ granulocytes was found to be present in the peripheral blood mononuclear cell (PBMC) fraction in humans. This population of granulocytes, termed low-density granulocytes (LDGs), was reported to be elevated and associated with disease activity or severity in a number of different conditions including SLE, asthma and HIV infection. However, both the frequency and clinical significance of LDGs associated with tuberculosis are unclear. Here we determined LDG levels and made comparisons between subjects with active pulmonary tuberculosis (PTB) and healthy controls, between PTB patients with mild-to-moderate disease and patients with advanced disease, and among PTB patients following anti-tuberculous therapy of varying durations. The direct correlation between M. tuberculosis infection and LDG levels was confirmed by in vitro infection of whole peripheral blood and isolated granulocytes with mycobacteria. Our results demonstrated that PBMCs in PTB patients contained significantly elevated percentages of LDGs compared with control subjects. LDGs in tuberculosis expressed higher levels of activation markers compared to normal-density granulocytes (NDGs). M. tuberculosis induced the generation of LDGs in both whole blood and isolated NDGs from control subjects, which suggests that LDGs associated with M. tuberculosis infection are likely to originate from in situ activation. Furthermore, our results revealed that the frequency of LDGs is associated with the severity of tuberculosis.
Macrophages display remarkable plasticity, with the ability to undergo dynamic transition between classically and alternatively activated phenotypes. Long non-coding RNAs (lncRNAs) are more than 200 nucleotides in length and play roles in various biological pathways. However, the role of lncRNAs in regulating macrophage polarization has yet to be explored. In this study, lncRNAs expression profiles were determined in human monocyte-derived macrophages (MDMs) incubated in conditions causing activation toward M(IFN-γ + LPS) or M(IL-4) phenotypes. Compared with primary MDMs, 9343 lncRNAs and 5903 mRNAs were deregulated in M(IFN-γ + LPS) group (fold change ≥2.0, P < 0.05), 4592 lncRNAs and 3122 mRNAs were deregulated in M(IL-4) group. RT-qPCR results were generally consistent with the microarray data. Furthermore, we found that TCONS_00019715 is expressed at a higher level in M(IFN-γ + LPS) macrophages than in M(IL-4) macrophages. TCONS_00019715 expression was decreased when M(IFN-γ + LPS) converted to M(IL-4) whereas increased when M(IL-4) converted to M(IFN-γ + LPS). Knockdown of TCONS_00019715 following the activation of THP-1 cellls using IFN-γ and LPS diminished the expression of M(IFN-γ + LPS) markers, and elevated the expression of M(IL-4) markers. These data show a significantly altered lncRNA and mRNA expression profile in macrophages exposure to different activating conditions. Dysregulation of some of these lncRNAs may play important roles in regulating macrophage polarization.
BackgroundIt is well-known that increased frequency of neutrophils was found in patients with systemic lupus erythematosus (SLE). However, the immunomodulatory roles and mechanisms of neutrophils in SLE are poorly understood.MethodsPatients with SLE were recruited from the First Affiliated Hospital of Nanchang University. The medical history, clinical manifestations, physical examination, laboratory measurements, therapeutic regimen and treatment response were recorded. The expression of costimulatory molecules including programmed death 1 (PD-1), programmed death ligand 1 (PD-L1), T-cell immunoglobulin and mucin domain–containing protein 3 (Tim-3), CD40, T cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory domains (TIGIT), CD80 and CD86 on neutrophils were determined by flow cytometry. The frequencies of PD-L1-expressing neutrophils in patients with SLE were further analyzed for their correlation with markers of autoimmune response, inflammation, disease activity and severity of SLE.ResultsThe frequency of PD-L1-expressing neutrophils was significantly elevated in SLE patients compared to the healthy controls (P < 0.0001). The frequency of PD-L1-expressing neutrophils in patients with SLE was increased significantly in subjects with high ANA titre, high anti-nRNP/Sm, high levels of inflammatory markers and high SLE Disease Activity Index (SLEDAI) score. Furthermore, the percentages of PD-L1-expressing neutrophils were significantly decreased in SLE patients that received a 15-day regular treatment with corticosteroids and immunosuppressive drugs (P = 0.0075).ConclusionThe frequency of PD-L1-expressing neutrophils is elevates in patients with SLE, correlates with the disease activity and severity of SLE, and may serves as a negative feedback mechanism preventing potential tissue damage caused by excessive autoimmune responses in patients with SLE.
Background Several studies have investigated the effect of non–vitamin K antagonist oral anticoagulants ( NOAC s) in atrial fibrillation ( AF ) patients with cancer, but the results remain controversial. Therefore, we conducted a meta‐analysis to compare the efficacy and safety of NOAC s versus warfarin in this population. Methods and Results We systematically searched the PubMed and Embase databases until February 16, 2019 for studies comparing the effect of NOAC s with warfarin in AF patients with cancer. Risk ratios ( RR s) with 95% CI s were extracted and pooled by a random‐effects model. Five studies involving 8908 NOAC s and 12 440 warfarin users were included. There were no significant associations between cancer status and risks of stroke or systemic embolism, major bleeding, or death in AF patients. Compared with warfarin, NOAC s were associated with decreased risks of stroke or systemic embolism ( RR , 0.52; 95% CI , 0.28–0.99), venous thromboembolism ( RR , 0.37, 95% CI , 0.22–0.63), and intracranial or gastrointestinal bleeding ( RR , 0.65; 95% CI , 0.42–0.98) and with borderline significant reductions in ischemic stroke ( RR , 0.63; 95% CI , 0.40–1.00) and major bleeding ( RR , 0.73; 95% CI , 0.53–1.00). In addition, risks of efficacy and safety outcomes of NOAC s versus warfarin were similar between AF patients with and without cancer. Conclusions In patients with AF and cancer, compared with warfarin, NOAC s had lower or similar rates of thromboembolic and bleeding events and posed a reduced risk of venous thromboembolism.
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