BMC Immunology最新文献

Background: Severe pneumonia (SP) poses a serious threat to patients' lives, and this study aimed to explore the diagnostic and prognostic value of miR-193b-3p on SP, thereby providing novel insights for the clinical management of SP.

Methods: The miR-193b-3p expression was evaluated by PCR. The diagnostic value of miR-193b-3p on SP was assessed by ROC. The association between miR-193b-3p expression and the SP severity was assessed by the correlation analysis. The correlation between miR-193b-3p expression and the survival status of SP patients was evaluated by the Kaplan-Meier survival analysis. Potential independent prognostic factors for SP were predicted by multivariate COX regression analysis. Bioinformatics analysis assessed the possible pathways regulated by miR-193b-3p.

Results: Upregulation of miR-193b-3p in SP patients showed a diagnostic value in SP. The miR-193b-3p expression was positively correlated with the levels of WBC, NEU, CRP, PCT, BNP, and D-D, and negatively correlated with LYM. The expression level of miR-193b-3p was significantly associated with the APACHE-II and CPIS scores, and a better survival rate was observed in SP subjects with low miR-193b-3p expression levels. MiR-193b-3p, together with CRP, PCT, APACHE-II, and CPIS, could also serve as independent prognostic factors for SP. MiR-193b-3p was associated with PI3K-Akt, MAPK, FoxO, TRP channel, and Wnt signaling pathways.

Conclusion: Upregulated miR-193b-3p expression in SP patients had a diagnostic and prognostic value for SP.

Background: Monocyte chemoattractant protein-1 (MCP-1) has been utilized as a prognostic indicator for sepsis patients; however, the findings have been inconsistent. This meta-analysis seeks to elucidate the prognostic significance of MCP-1 in individuals diagnosed with sepsis.

Methods: We systematically queried four databases (Web of Science, PubMed, EMBASE, Cochrane Library) to identify studies published from the establishment of the databases until January 2025. Hazard ratios (HRs) with 95% CIs were employed to evaluate the prognostic significance of MCP-1 in this patient population. In our study, the Newcastle-Ottawa Quality Assessment Scale was evaluated for quality assessment, and Funnel plot was used for publication offset.

Results: A total of 592 patients from eight studies were included in the evaluation. The findings revealed that MCP-1 levels were significantly elevated in non-survivors compared to those who survived [SMD = 0.54, 95% CI: 0.25-0.82, P = 0.0002]. Our study demonstrated that elevated levels of MCP-1 were significantly associated with an unfavorable prognosis in patients with sepsis, with a hazard ratio (HR) of 1.36 (95% confidence interval: 1.25-1.48; P < 0.00001) using a random-effects model. The funnel plot indicated no publication bias.

Conclusion: This meta-analysis suggests that elevated levels of MCP-1 could serve as a valuable prognostic indicator in sepsis patients, however, this conclusion still requires validation through higher-quality studies with longer-term follow-up.

N6-methyladenosine (m6A) modification plays a critical role in lipid metabolism, yet the mechanism by which the m6A demethylase Fat mass and obesity-associated protein (FTO) regulates hepatic steatosis and autophagy remains unclear. This study aimed to investigate whether FTO modulates lipid metabolism and autophagy through m6A-dependent regulation of Beclin-1 (BECN1). In vitro, HepG2 cells were treated with free fatty acids (FFA) to establish a lipid overload model. Lipid levels were measured enzymatically; autophagy markers were assessed by Western blot; m6A modification was evaluated via dot blot, MeRIP, and RIP assays; and RNA stability was determined using actinomycin D. In vivo, high-fat diet (HFD)-fed mice were established. Liver histology and lipid profiles were analyzed. FFA treatment reduced global m6A levels and upregulated FTO expression. FTO knockdown attenuated lipid accumulation, improved dyslipidemia, and restored autophagy in HepG2 cells. Mechanistically, FTO directly bound to BECN1 mRNA and demethylated it at the adenine-567 site, thereby inhibiting its stability and expression. Rescue experiments confirmed that BECN1 knockdown reversed the beneficial effects of FTO silencing on lipid metabolism and autophagy. In HFD-fed mice, hepatic FTO knockdown ameliorated steatosis and improved serum and hepatic lipid levels. In conclusion, FTO deficiency enhances BECN1 m6A methylation and mRNA stability, promoting autophagy and ameliorating lipid accumulation. These findings identify FTO as a potential therapeutic target for treating hyperlipidemia and related metabolic disorders.

In addition to chromosomal abnormalities, excessive systemic or local inflammation, particularly in the uterus, may also contribute to the pathogenesis of early pregnancy loss. Recently, several systemic immune inflammation indices, including the systemic immune-inflammation index (SII), the systemic inflammation response index (SIRI), the neutrophil-to-lymphocyte ratio (NLR), and the pan-immune inflammation value (PIV), have been used as potential predictive markers for complicated pregnancies. Early pregnancy loss is associated with an inappropriate inflammatory response in pregnancy. In this retrospective study, we investigated whether these systemic immune inflammation indices are associated with the onset of early pregnancy loss. Six hundred sixty-three women with early pregnancy loss and 700 women without pregnancy complications across gestation were included. Data on complete blood tests were collected at the time of diagnosis, and the immune inflammation indices were calculated and analyzed. Women with early pregnancy loss had significantly decreased counts of total white cells, neutrophils, lymphocytes, monocytes, and platelets. However, the inflammation response indices, SII, SIRI, and NLR, but not PIV, in women with early pregnancy loss did not differ significantly from those in the controls. The predictive probability of early pregnancy loss was 58% using the combined four systemic inflammation indices, which had limited predictive power. In conclusion, our findings suggest that systemic inflammation, as measured by peripheral blood tests, is not strongly associated with early pregnancy loss.

Background: Metabolic-associated fatty liver disease (MAFLD) is a liver disease characterized by abnormal lipid metabolism. This study investigated the effects of succinylation on hepatocyte steatosis and lipid storage in MAFLD in vitro.

Methods: mRNA and protein levels of two desuccinylases (SIRT5 and SIRT7) and three succinylases (KAT2A, KAT3B, and CPT1A) were evaluated in blood samples from MAFLD patients. Exposure of HepG2 and Huh7 cells to free fatty acids (FFA) was established to mimic MAFLD in vitro. Triglyceride (TG) content, total cholesterol (TC) content, and lipid accumulation were combined to evaluate lipid metabolism. HSPD1 protein was pulled-down using immunoprecipitation (IP). Co-immunoprecipitation (co-IP) combined with immunofluorescence was used to verify the interaction between SIRT5 and HSPD1.

Results: SIRT5 was prominently down-regulated in blood samples of patients with MAFLD. FFA exposure induced lipid metabolism dysfunction by increasing TC, TG levels, and the number of Oil Red O and BODIPY-stained lipid droplets. Overexpression of SIRT5 significantly attenuated the effects of FFA on lipid metabolism. HSPD1 was found to interact with SIRT5, which mediated HSPD1 desuccinylation and accelerated its protein degradation. Overexpression of HSPD1 sharply reversed the protective effects of elevated SIRT5 on cellular steatosis in HepG2 and Huh7 cells. SIRT5 directly interacted with HSPD1, and elevated SIRT5 levels reduced HSPD1 protein stability through desuccinylation modification.

Conclusion: SIRT5-mediated desuccinylation of HSPD1 protects against hepatic steatosis in MAFLD model cells, suggesting that targeting SIRT5 and HSPD1 may represent a novel therapeutic strategy for preventing and treating MAFLD.

Background: Psoriasis is a prevalent autoimmune skin disorder; however, the mechanism of its pathogenesis remains fully understood. The imbalance of regulatory T (T_reg) cells and effector T cells represents one potential mechanism, where a low dose of IL-2 is important.

Aim of the work: Given that IL-2/IL-12 complex is considered as an immune modulator for antigen-activated lymphocyte proliferation, this study aimed to compare the immunophenotypic, clinical, and histological effects of anti-IL-2/IL-2 complex to a low dose of free IL-2 on experimental psoriasis-like skin inflammation induced by imiquimod.

Materials and methods: Thirty-five Balb/c male mice were left without treatment, or were received topical application of imiquimod (IMQ, 3.125 mg/mouse) to induce psoriasis-like skin inflammation, and then the mice were treated with intraperitoneal (i.p.) injection of 100 µL containing anti-IL-2/IL-2 complex (2.5 µg /0.5 µg/mouse), or topical steroids (62.50 mg/mouse), or low dose of free IL-2 (i.p.; 0.5 µg/mouse). The expression levels of CD4, CD25, and Foxp3 in the leukocytes were assessed by multiparametric flow cytometry. The effects of different treatments on the histology and pathology of the induced psoriasis were also assessed.

Results: IMQ-induced hyperkeratosis, parakeratosis and mild papillomatosis with the retained nuclei in the keratin layer, whereas acanthosis with exocytosis was prominent in the epidermal layer. Lymphocyte infiltration was profusely all over the dermis. Additionally, there were some degrees of Munro micro abscesses were observed in the keratin layer with a collection of neutrophils in the group treated with standard betamethasone cream which showed mild improvement clinically, histopathological with no significant difference between this group and the naïve and positive control groups. After 7 days from the onset of treatment, we found that treatment of mice with anti-IL-2/IL-2 complex decreased the thickness of the epiderms as compared to their groups. Furthermore, the relative number of CD4⁺Foxp3⁺CD25⁺ cells showed increases in psoriasis mice treated with anti-IL-2/IL-2 complex as compared to other groups.

In conclusion: Anti IL-2/IL-2 complex therapy effectively ameliorated the clinical manifestations of psoriasis, with no apparent side effects, providing a new strategy for treating psoriasis.

Background: Despite promising clinical data for Toll-like receptor-9 agonists encapsulated in virus-like particles (TLR9a VLPs), the relative potency and mechanisms of TLR7a and dual TLR7/8a VLPs remain undefined. TLR9a VLPs, also known as Vidutolimod or CMP-001 is a novel TLR9a encapsulated in Qβ VLPs, which can activate plasmacytoid DCs (pDCs) and promote T cell activation. Other endosomal TLRs such as TLR7 and TLR8 expressed in DCs have been studied in several preclinical and clinical studies; however, their immune-activating properties when encapsulated in VLPs have not been tested before. Here, we utilized a series of in vitro experiments to test and compare immune cell activation stimulated by agonists to TLR7 (TLR7a), TLR7/8 (TLR7/8a), and TLR9 (TLR9a) when encapsulated in Qβ VLPs.

Methods: Activation of immune cells (monocytes, natural killer (NK) cells, T cells, pDCs, and monocytic DCs (mDCs)) in response to TLR7a, TLR7/8a and TLR9a VLPs, was evaluated using flow cytometry, intracellular cytokine staining (ICS) and ELISA. Neutralizing cytokine antibodies, immune cell depletion kits and transwell models were used to determine the contribution of select cytokines and antigen presenting cells (APCs) in VLP-mediated immune cell activation.

Results: Results showed that all three VLPs activated pDCs and monocytes. However, TLR7/8a VLPs were most effective at NK and T cell activation compared to the other VLPs. NK cells were a major source of IFNγ, whereas pDCs were the main source of IFNα and TNFα production in response to the VLPs. Neutralizing antibodies against TNFα (but not IFNα) showed significant suppressive effects on TLR7/8a VLP-mediated activation of CD4 + and CD8 + T cells. Depletion of APCs completely abrogated TLR7/8 VLP-mediated activation of CD4 + and CD8 + T cells. Lastly, TLR7/8a VLP-mediated activation of T cells was highly dependent on direct contact with pDCs (and not DC1 and DC2 subsets).

Conclusions: In summary, endosomal TLRa VLPs all have the ability to activate pDCs, however, combined TLR7/8 activation using TLR7/8a VLPs was significantly more effective than the other VLPs at activating T cells and was dependent on direct contact with pDCs. Therefore, TLR7/8a VLPs may potentially induce a robust anti-tumor immune response and warrant further investigation for cancer therapy.

Objective: Based on the bidirectional relationship between sleep and macrophages in healthy and diseased states, this systematic review and meta-analysis investigated the effect of disrupted sleep on macrophage polarization.

Methods: A literature search was conducted in PubMed, Scopus, and Web of Science (WoS) databases up to October 2023, identifying English-language studies on disrupted sleep's effects on macrophage polarization. After screening and data extraction, the standardized mean difference (SMD) with a 95% Confidence Interval (CI) was calculated for M1 pro-inflammatory and M2 anti-inflammatory markers. Heterogeneity was assessed using Cochran's Q test and the I-square (I²) statistic, and subgroup analyses were performed. The methodological quality was assessed using SYRCLE's RoB tool. Publication bias was examined through Egger's test and the trim-and-fill method, and a sensitivity analysis was also conducted. The meta-analysis was performed using STATA version 14.2 software.

Results: Thirteen studies were included. Results indicated that disrupted sleep significantly increased CD11c levels [SMD: 2.450, 95% CI: 1.517 to 3.383, I² = 11.7%], and decreased CD206 levels [SMD: -2.616, 95% CI: -4.911 to -0.321, I² = 83.3%]. The association between disrupted sleep and M1/M2 was uncertain, with sex identified as a potential source of heterogeneity. No publication bias or sensitivity was detected, which strengthens the reliability and robustness of the findings.

Conclusion: Disrupted sleep significantly influenced macrophage polarization towards a CD11c⁺ M1 inflammatory phenotype. Given the heterogeneity and limited number of studies, these findings should be interpreted as exploratory. Further research on the underlying mechanisms, particularly concerning biological sex, to better understand sleep's impact on immune function and treatment strategies for inflammatory conditions.

Background: The clinical presentation of COVID-19 varies significantly by viral variant; the Delta variant often causes severe lung inflammation, whereas Omicron tends to result in less severe respiratory disease but may more readily affect other organs. The autoimmune mechanisms behind these variant-specific complications, particularly the potential role of anti-neutrophil cytoplasmic (ANCA) antibodies, are still not well defined. This study investigated myeloperoxidase (MPO), proteinase 3 (PR3), and glomerular basement membrane (GBM) antibodies in patients infected with the Delta and Omicron SARS-CoV-2 variants to evaluate their associations with specific clinical complications, such as renal or respiratory involvement.

Methods: Samples were collected during Delta and Omicron outbreaks from hospitalized COVID-19 patients (40 Delta, 40 Omicron) and 40 healthy controls. Serum autoantibodies (MPO, PR3, GBM) were measured via ELISA, and laboratory/clinical data were collected.

Results: All autoantibody levels remained within normal limits. Despite statistical significance (P < 0.05), effect sizes were small (η²=0.085-0.180). Anti-MPO was highest in the Delta group (1.08 U/mL) vs. Control (0.71 U/mL) and Omicron (0.77 U/mL). Anti-PR3 was lowest in the Delta group (0.83 U/mL) vs. Control (1.52 U/mL). Anti-GBM was lowest in the Omicron group (1.48 U/mL) vs. Control (3.48 U/mL) and Delta (3.10 U/mL). Clinically, the Delta group exhibited significantly lower oxygen saturation (92.28% ± 8.69) than the Omicron group (96.15% ± 2.77; P = 0.009). Markers of inflammation and tissue damage-including C-reactive protein (CRP), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and coagulation parameters-were markedly elevated in the Delta group compared to the Omicron group (P < 0.001). Conversely, creatinine was significantly higher in the Omicron group (P < 0.001).

Conclusion: While autoantibody levels remained normal, clinical profiles diverged significantly between variants. The Delta variant was associated with heightened systemic inflammation, whereas Omicron was associated with greater organ involvement, suggesting the possibility of distinct pathogenic mechanisms.