Innate Immunity最新文献

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is the leading cause of hospitalization and mortality in COPD patients. The occurrence of antibiotic resistance and the progression of non-infectious diseases contribute to poor patient outcomes. Thus, a comprehensive understanding of the mechanisms underlying AECOPD is essential for effective prevention. It is widely acknowledged that the immune system plays a fundamental role in pathogen clearance and the development of inflammation. Immune dysregulation, either due to deficiency or hyperactivity, has been implicated in AECOPD pathogenesis. Therefore, the purpose of this review is to investigate the possible mechanisms underlying dysregulated immune function and disease progression in COPD patients, specifically focusing on the innate and adaptive immune responses. The ultimate aim is to provide new insights for clinical prevention and treatment strategies targeting AECOPD.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that primarily affects the synovial joint linings, resulting in progressive disability, increased mortality, and considerable economic costs. Early treatment with disease-modifying antirheumatic medications (DMARDs) can significantly improve the overall outlook for people with RA. Contemporary pharmaceutical interventions, encompassing standard, biological, and emerging small molecule disease- modifying anti-rheumatic medications continue to be the cornerstone of RA management, with substantial advancements made in the pursuit of achieving remission from the disease and preventing joint deformities. Nevertheless, a substantial segment of individuals with RA do not experience a satisfactory response to existing treatments, underscoring the pressing need for novel therapeutic options. Biologic DMARDs are among the therapy choices. Non-tumor necrosis factor inhibitors (Non-TNFi) such as abatacept, rituximab, tocilizumab, and sarilumab are examples, as are anti-tumor necrosis factor (TNF) medications such as infliximab, adalimumab, etanercept, golimumab, and certolizumab pegol. More recent biomarkers have emerged and showed usefulness in the early detection of RA. These biomarkers, often referred to simply as "biomarkers", are quantifiable indicators of normal or pathologic processes, and they can also gauge treatment response. The assessment of RA treatment response typically combines patient-reported outcomes, physical evaluations, and laboratory findings, as there isn't a single biomarker that has proven sufficient for measuring disease activity. This review explores the usage of biologic DMARDs as a therapeutic approach for RA, as well as the biomarkers typically used for RA early diagnosis, prognosis prediction, and disease activity evaluation.

BackgroundPrevious studies suggest that transient receptor potential melastatin 2 (TRPM2) plays a protective role in sepsis by enhancing bacterial clearance. This effect is mediated through the modulation of macrophage phenotypic changes, which strengthen the immune response against infection. However, the specific role and underlying mechanism of TRPM2 in macrophage polarization during sepsis remain unclear.MethodCecal ligation and puncture (CLP) was used to establish a mouse sepsis model, and bone marrow-derived macrophages (BMDMs) and peritoneal macrophages were prepared from C57BL/6 wild-type and TRPM2 knockout (trpm2^-/-) mice. IPI549 was utilized as a specific inhibitor of PI3K. Macrophage polarization, bactericidal ability, and the PI3K/protein kinase B (AKT)/cyclic adenosine monophosphate response element-binding protein signaling pathway were assessed. In addition, survival rate, bacterial burden, lung wet/dry weight ratio, lung and liver injury scores, and cytokine levels were measured in CLP-induced septic mice.ResultsIn lipopolysaccharide (LPS)-stimulated BMDMs, trpm2 deficiency increased the expression of characteristic markers associated with the M2b phenotype, reduced the bactericidal ability, and activated the PI3K/AKT/CREB signaling pathway. Consequently, both trpm2^-/- BMDMs and trpm2^-/- mice exhibited impaired bactericidal clearance during CLP-induced sepsis. Furthermore, IPI549 attenuated TRPM2 deletion-induced M2b polarization and restored the bactericidal function of BMDMs. Notably, IPI549 preconditioning reversed the increased susceptibility of the trpm2^-/- mice to sepsis. The 7-day mortality rate was 92% in trpm2^-/- mice, compared to 42% in IPI549-pretreated trpm2^-/- mice. Moreover, IPI549-treated mice exhibited improved lung wet/dry ratios, reduced lung and liver injury scores, reversed M2b polarization and decreased bacterial load.ConclusionThe PI3K/AKT/CREB pathway mediates the effect of TRPM2 by inhibiting M2b macrophage polarization and promoting bacterial clearance during sepsis.

ObjectiveTo research whether radiation-induced liver damage and fibrosis could be mitigated by resveratrol (RSV) and to elucidate its underlying mechanism.MethodsA radiation-induced liver damage (RILD) model of murine was constructed. RSV was used as an intervention agent. The effects of RSV on inflammatory reaction, apoptosis, senescence, fibrosis, survival, and liver functions were detected by β-Gal, Sirius red, Masson's trichrome, and Tunnel staining using an automated biochemistry analyzer. The protein expression levels of P16 and P21 were detected by Western blot.ResultsRSV alleviated inflammatory injury of RILD mice. RSV decreased the serum pro-inflammatory cytokines of RILD mice. RSV alleviated radiation-induced hepatocellular senescence. The protein expression levels of P16 and P21 in RILD mice were decreased with RSV administration. RSV decreased the number of apoptotic cells in the early stage of RILD. RSV alleviated liver fibrosis and liver function in RILD mice.ConclusionsRSV reduces RILD and fibrosis, and may be related to inhibiting cellular aging and reducing inflammation.

The application of biological therapy and glucocorticoids in Auto-immune diseases (AID) patients will cause immunocompromised host (ICH) prone to infection. And monocytes play a key role in both innate and adaptive immune responses. We aimed to investigate the changes of circulating monocyte subsets in AID or AID-ICH patients with pulmonary infection. The subgroups and PD-L1 expression of monocytes were measured by flow cytometry in healthy individuals (HC), new-onset AID patients (AID cohort) and AID-ICH patients with pulmonary opportunistic infection (AID-ICH cohort). Flow cytometry analysis was used to determine the distribution of monocyte subsets, including classical monocytes (CL, CD14⁺⁺CD16^-), intermediate monocytes (ITM, CD14⁺⁺CD16⁺) and non-classical monocytes (NC, CD14^+/-CD16⁺⁺), as well as the dynamic change of PD-L1 ⁺cluster among monocyte subsets. Among total monocyte, AID-ICH displayed decreased CL subset along with increased NC subset compared to HCs and AID. Regarding PD-L1 ⁺monocytes, although CL subset constituted the majority of that in HCs, AIDs and AID-ICHs, imbalance of NC/CL within PD-L1 ⁺monocytes was only noticed in AID-ICHs (P < 0.05). Furthermore, when AID subjects were developed into immunocompromised status (ICH), PD-L1 ⁺cluster in CL was minorly decreased (P > 0.05). Clinically, the lower ratio of PD-L1 ⁺cluster among CL subset (P < 0.05) and the less differentiated CL in PD-L1 ⁺monocytes (P < 0.05) was more likely to leaded to disease progression. The imbalance of circulating NC/CL subset was remarkable in immunocompromised host with pulmonary opportunistic infection, especially involvement of PD-L1⁺ cluster, which served as a potential biomarker in clinical practice.

Background: Killer immunoglobulin-like receptors (KIRs) are key molecules used by natural killer (NK) cells to interact with target cells. These receptors exhibit extensive genotypic polymorphism which has been associated with varying outcomes in immune responses against diseases. This study aimed to investigate the relationships between KIR genotypes and haplotypes with acute lymphoblastic leukemia (ALL) in Saudi patients.

Methods: A total of 259 Saudi subjects including 145 cases of acute lymphoblastic leukemia (ALL) and 114 healthy controls living in Riyadh were genotyped for 16 KIR genes and the two HLA-C1 and -C2 allotypes using PCR-SSP genotyping method.

Results: A significant high frequency of the two inhibitory KIR genes; 2DL1 (OR = 2.4; p < 0.0001) and 3DL1(OR = 10.87; p = 0.0068) in ALL compared to healthy group was observed. In contrast, the activating 2DS4 gene was significantly higher in healthy controls (OR = 0.15, p < 0.0001) compared to ALL patients. Haplotype analysis shows that BX haplogroup was strongly associated with the occurrence of ALL (OR = 4.39; p < 0.0001). Further combinatory analysis of KIR genes with their HLA-C1 and -C2 ligands demonstrated strong statistically protective effect of the 2DS1-C2 combination from ALL (OR = 0.06; p = 0.0003).

Conclusion: This study presents strong evidence supporting the connection between certain KIR genotypes, haplotypes, and KIR-HLA combinations with acute ALL in the Saudi population. The heightened occurrence of inhibitory KIR genes (2DL1 and 3DL1) and the BX haplotype in ALL patients indicates a possible involvement of these genetic variability with the dysfunctional of NK cells in the context of ALL disease.

Immune cells are heterogeneous and perform different functions in different microenvironment, thus playing different roles in different stages of diseases. Studies have shown that immune cells are involved in the pathogenesis of many diseases, and there is a causal association of immune cells with disease states. Signaling Lymphocyte Activation Molecule family (SLAMF) members are a newly appreciated group of specific receptors that are mainly expressed in immune cells and whose role is to regulate the function of immune cells. SLAMF7, also known as CD319, has been widely reported in multiple myeloma, and in recent years, more and more studies have shown that SLAMF7 is widely involved in the function of immune cells and the progression of breast cancer, acquired immune deficiency syndrome, systemic lupus erythematosus and other immune cells-related diseases. However, the mechanisms underlying the regulatory role of SLAMF7 on immune cells, and the impact on the progression of immune cells-related diseases remain poorly elucidated. In this review, we summarize current knowledge about the role of SLAMF7 in immune cells and related diseases such as cancer, infectious disease, autoimmune disease and atherosclerosis, and the therapeutic strategy targeting SLAMF7 is also described. By better understanding the role and regulation of SLAMF7, we hope to provide new insights and directions for improving the diagnosis and treatment of inflammation.

Mastitis in cattle poses a significant health challenge and results in substantial economic losses for the dairy industry. This study aimed to extend the existing precision-cut bovine udder slices (PCBUS) model as an in vitro model to explore the potential of inducing trained immunity in the udder with the goal to use the resulting knowledge for potential new treatment strategies. Interestingly, incubation of PCBUS with 10% fetal calf serum (FCS), but no 2% or FCS-free, negatively affected the production of some of the chemokines/cytokines analysed. When trained immunity was induced by zymosan, followed by stimulation with E. coli-derived lipopolysaccharide (LPS), production of interleukin (IL)-1β, IL-6, tumor necrosis factor α and interferon (IFNγ) was downregulated while production of IL-17A and pro-resolving lipid mediators (leukotrienes and prostaglandins) was upregulated. While the current experimental setup did not definitively confirm the induction of trained immunity for all parameters analysed in PCBUS, it validated the utility of PCBUS as a robust in vitro model for studying bovine udder inflammation. This model offers a promising platform for developing innovative mastitis treatments, particularly given the growing concern over antimicrobial resistance, as well as offering alternatives to the use of live animals in experimental studies in line with the 3Rs principles. It also provides a valuable tool for advancing our understanding of immune responses in the bovine udder. By adapting the precision-cut tissue slice technique to bovine udders, this model enables extensive research into new therapeutic approaches and supports basic research efforts to characterise complex pathophysiological processes associated with mastitis. Furthermore, our data highlight the potential limitations of FCS in in vitro studies. Our data should not only stimulate the discussion about FCS in homologues or heterologues species, but should also be kept in mind regarding the need for foetal calves to generate FCS in line with the 3Rs guideline.

This study aimed to investigate the impact of Cardamine violifolia on muscle protein degradation, the inflammatory response and antioxidant function in weaned piglets following LPS challenge. Twenty-four weaned piglets were used in a 2 × 2 factorial experiment with dietary treatment (sodium selenite or Cardamine violifolia) and LPS challenge. After 28 days of feeding, pigs were injected intraperitoneally with 100 μg/kg LPS or saline. Dietary supplementation with Cardamine violifolia mitigated the reduction in insulin and growth hormone levels induced by LPS. It also curbed the LPS-induced elevation of plasma glucagon, urea nitrogen, and creatinine concentrations. Cardamine violifolia reduced muscle damage caused by LPS, as evidenced by increased protein content and protein/DNA ratio and decreased TNF-α and IL-1β mRNA expression. Furthermore, Cardamine violifolia modulated the expression of FOXO1, FOXO4, and MuRF1 in muscle, indicative of the protective effect against muscle protein degradation. Enhanced muscle antioxidant function was observed in the form of increased T-AOC, reduced MDA concentration, and decreased mRNA expression of GPX3, DIO3, TXNRD1, SELENOS, SELENOI, SELENOO, and SEPHS2 in LPS-treated piglets. The findings suggest that Cardamine violifolia supplementation can effectively alleviate muscle protein degradation induced by LPS and enhance the antioxidant capacity in piglets.