BMC Immunology最新文献

Background: Control of Tuberculosis (TB) infection is mainly the result of productive teamwork between T-cell populations and antigen presenting cells (APCs). However, APCs activation at the site of initiating cellular immune response during BCG early infection is not completely understood.

Methods: In this study, we injected C57BL/6 mice in intravenous (i.v) or subcutaneous (s.c) route, then splenic or inguinal lymph node (LN) DCs and MΦs were sorted, and mycobacteria uptake, cytokine production, antigen presentation activity, and cell phenotype were investigated and compared, respectively.

Results: Ag85A-specific T-cell immune response began at 6 days post BCG infection, when BCG was delivered in s.c route, Th17 immune response could be induced in inguinal LN. BCG could induce high level of activation phenotype in inguinal LN MΦs, while the MHC II presentation of mycobacteria-derived peptides by DCs was more efficient than MΦs.

Conclusions: The results showed that BCG immunized route can decide the main tissue of T-cell immune response. Compared with s.c injected route, APCs undergo more rapid cell activation in spleen post BCG i.v infection.

Background and aim: Liver failure, which is predominantly caused by hepatitis B (HBV) can be improved by an artificial liver support system (ALSS). This study investigated the phenotypic heterogeneity of immunocytes in patients with HBV-related acute-on-chronic liver failure (HBV-ACLF) before and after ALSS therapy.

Methods: A total of 22 patients with HBV-ACLF who received ALSS therapy were included in the study. Patients with Grade I according to the ACLF Research Consortium score were considered to have improved. Demographic and laboratory data were collected and analyzed during hospitalization. Immunological features of peripheral blood in the patients before and after ALSS were detected by mass cytometry analyses.

Results: In total, 12 patients improved and 10 patients did not. According to the immunological features data after ALSS, the proportion of circulating monocytes was significantly higher in non-improved patients, but there were fewer γδT cells compared with those in improved patients. Characterization of 37 cell clusters revealed that the frequency of effector CD8⁺ T (P = 0.003), CD4⁺ T_CM (P = 0.033), CD4⁺ T_EM (P = 0.039), and inhibitory natural killer (NK) cells (P = 0.029) decreased in HBV-ACLF patients after ALSS therapy. Sub group analyses after treatment showed that the improved patients had higher proportions of CD4⁺ T_CM (P = 0.010), CD4⁺ T_EM (P = 0.021), and γδT cells (P = 0.003) and a lower proportion of monocytes (P = 0.012) compared with the non-improved patients.

Conclusions: Changes in effector CD8⁺ T cells, effector and memory CD4⁺ T cells, and inhibitory NK cells are associated with ALSS treatment of HBV-ACLF. Moreover, monocytes and γδT cells exhibited the main differences when patients obtained different prognoses. The phenotypic heterogeneity of lymphocytes and monocytes may contribute to the prognosis of ALSS and future immunotherapy strategies.

Multi-epitope polypeptide vaccines, a fusion protein, often have a string-of-beads system composed of various specific peptide epitopes, potential adjuvants, and linkers. When choosing the sequence of various segments and linkers, many alternatives are available. These variables can influence the vaccine's effectiveness through their effects on physicochemical properties and polypeptide tertiary structure.The most conserved antigens were discovered using BLASTn. To forecast the proteins' subcellular distribution, PSORTb 3.0.2 was used. Vaxign was used for the preliminary screening and antigenicity assessment. Protein solubility was also predicted using the ccSOL omics. Using PRED-TMBB, it was anticipated that the protein would localize across membranes. The IEDB and BepiPred-2.0 databases were used to predict the immunogenicity of B cell epitopes. A multi-epitope construct was developed and analyzed to evaluate. Twenty epitopes from A. baumannii's outer membrane protein (omp) were included in the vaccination. TLR4 agonist explosibility was investigated. The physicochemical characteristics, secondary and tertiary structures, and B-cell epitopes of vaccine constructs were assessed. Additionally, docking and MD experiments were used to examine the relationship between TLR4 and its agonist.Thirteen antigens were discovered, and eight of the 13 chosen proteins were predicted to be surface proteins. The 34 kDa outer membrane protein, Omp38, Omp W, CarO, putative porin, OmpA, were chosen as having the right antigenicity (≥0.5). FhuE and CdiA were eliminated from further study because of their low antigenicity. The vaccine design was developed by combining the most effective 10 B-cell and 10 MHC-I/MHCII combined coverage epitopes. The molecular formula of the vaccine was determined to be C1718H2615N507O630S17. The vaccine form has a molecular weight of 40,996.70 Da and 47 negatively charged residues (Asp + Glu), whereas 28 positively charged residues (Arg + Lys). The estimated half-life was 7.2 hours (mammalian reticulocytes, in vitro), > 20 hours (yeast, in vivo) and > 10 hours (Escherichia coli, in vivo) for the vaccine. The multi-epitope vaccine insertion is carried via the expression vector pcDNA3.1 (+).The multi-epitope vaccine may stimulate humoral and cellular immune responses, according to our findings, and it may be a candidate for an A. baumannii vaccine.

Background: SARS-CoV-2 remains a world-wide health issue. SARS-CoV-2-specific immunity is induced upon both infection and vaccination. However, defining the long-term immune trajectory, especially after infection, is limited. In this study, we aimed to further the understanding of long-term SARS-CoV-2-specific immune response after infection.

Results: We conducted a longitudinal cohort study among 93 SARS-CoV-2 recovered individuals. Immune responses were continuously monitored for up to 20 months after infection. The humoral responses were quantified by Spike- and Nucleocapsid-specific IgG levels. T cell responses to Spike- and non-Spike epitopes were examined using both intercellular cytokine staining (ICS) assay and Activation-Induced marker (AIM) assay with quantification of antigen-specific IFNγ production. During the 20 months follow-up period, Nucleocapsid-specific antibody levels and non-Spike-specific CD4 + and CD8 + T cell frequencies decreased in the blood. However, a majority of participants maintained a durable immune responses 20 months after infection: 59% of the participants were seropositive for Nucleocapsid-specific IgG, and more than 70% had persisting non-Spike-specific T cells. The Spike-specific response initially decreased but as participants were vaccinated against COVID-19, Spike-specific IgG levels and T cell frequencies were boosted reaching similar or higher levels compared to 1 month post-infection. The trajectory of infection-induced SARS-CoV-2-specific immunity decreases, but for the majority of participants it persists beyond 20 months. The T cell response displays a greater durability. Vaccination boosts Spike-specific immune responses to similar or higher levels as seen after primary infection.

Conclusions: For most participants, the response persists 20 months after infection, and the cellular response appears to be more long-lived compared to the circulating antibody levels. Vaccination boosts the S-specific response but does not affect the non-S-specific response. Together, these findings support the understanding of immune contraction, and with studies showing the immune levels required for protection, adds to the knowledge of durability of protection against future SARS-CoV-2.

Background: In recent years, research on the pathogenesis of systemic lupus erythematosus (SLE) has made great progress. However, the prognosis of the disease remains poor, and high sensitivity and accurate biomarkers are particularly important for the early diagnosis of SLE.

Methods: SLE patient information was acquired from three Gene Expression Omnibus (GEO) databases and used for differential gene expression analysis, such as weighted gene coexpression network (WGCNA) and functional enrichment analysis. Subsequently, three algorithms, random forest (RF), support vector machine-recursive feature elimination (SVM-REF) and least absolute shrinkage and selection operation (LASSO), were used to analyze the above key genes. Furthermore, the expression levels of the final core genes in peripheral blood from SLE patients were confirmed by real-time quantitative polymerase chain reaction (RT-qPCR) assay.

Results: Five key genes (ABCB1, CD247, DSC1, KIR2DL3 and MX2) were found in this study. Moreover, these key genes had good reliability and validity, which were further confirmed by clinical samples from SLE patients. The receiver operating characteristic curves (ROC) of the five genes also revealed that they had critical roles in the pathogenesis of SLE.

Conclusion: In summary, five key genes were obtained and validated through machine-learning analysis, offering a new perspective for the molecular mechanism and potential therapeutic targets for SLE.

Background: Glucocorticoids are the first-line treatment for Pemphigus vulgaris (PV), but its serious side effects can be life-threatening for PV patients. Tacrolimus (FK506) has been reported to have an adjuvant treatment effect against PV. However, the mechanism underlying the inhibitory effect of FK506 on PV-IgG-induced acantholysis is unclear.

Objective: The objective of this study was to explore the effect of FK506 on desmoglein (Dsg) expression and cell adhesion in an immortalized human keratinocyte cell line (HaCaT cells) stimulated with PV sera.

Methods: A cell culture model of PV was established by stimulating HaCaT cells with 5% PV sera with or without FK506 and clobetasol propionate (CP) treatment. The effects of PV sera on intercellular junctions and protein levels of p38 mitogen-activated protein kinase (p38MAPK), heat shock protein 27 (HSP27), and Dsg were assayed using western blot analysis, immunofluorescence staining, and a keratinocyte dissociation assay.

Results: PV sera-induced downregulation of Dsg3 was observed in HaCaT cells and was blocked by FK506 and/or CP. Immunofluorescence staining revealed that linear deposits of Dsg3 on the surface of HaCaT cells in the PV sera group disappeared and were replaced by granular and agglomerated fluorescent particles on the cell surface; however, this effect was reversed by FK506 and/or CP treatment. Furthermore, cell dissociation assays showed that FK506 alone or in combination with CP increased cell adhesion in HaCaT cells and ameliorated loss of cell adhesion induced by PV sera. Additionally, FK506 noticeably decreased the PV serum-induced phosphorylation of HSP 27, but had no effect on p38MAPK phosphorylation.

Conclusion: FK506 reverses PV-IgG induced-Dsg depletion and desmosomal dissociation in HaCaT cells, and this effect may be obtained by inhibiting HSP27 phosphorylation.

Background: Lymphedema is an intractable disease that can be caused by injury to lymphatic vessels, such as by surgical treatments for cancer. It can lead to impaired joint mobility in the extremities and reduced quality of life. Chronic inflammation due to infiltration of various immune cells in an area of lymphedema is thought to lead to local fibrosis, but the molecular pathogenesis of lymphedema remains unclear. Development of effective therapies requires elucidation of the immunological mechanisms involved in the progression of lymphedema. The complement system is part of the innate immune system which has a central role in the elimination of invading microbes and acts as a scavenger of altered host cells, such as apoptotic and necrotic cells and cellular debris. Complement-targeted therapies have recently been clinically applied to various diseases caused by complement overactivation. In this context, we aimed to determine whether complement activation is involved in the development of lymphedema.

Results: Our mouse tail lymphedema models showed increased expression of C3, and that the classical or lectin pathway was locally activated. Complement activation was suggested to be involved in the progression of lymphedema. In comparison of the C3 knockout (KO) mouse lymphedema model and wild-type mice, there was no difference in the degree of edema at three weeks postoperatively, but the C3 KO mice had a significant increase of TUNEL⁺ necrotic cells and CD4⁺ T cells. Infiltration of macrophages and granulocytes was not significantly elevated in C3 KO or C5 KO mice compared with in wild-type mice. Impaired opsonization and decreased migration of macrophages and granulocytes due to C3 deficiency should therefore induce the accumulation of dead cells and may lead to increased infiltration of CD4⁺ T cells.

Conclusions: Vigilance for exacerbation of lymphedema is necessary when surgical treatments have the potential to injure lymphatic vessels in patients undergoing complement-targeted therapies or with complement deficiency. Future studies should aim to elucidate the molecular mechanism of CD4⁺ T cell infiltration by accumulated dead cells.

Objective: This systematic review aimed to map the evidence evaluated the relationship between vitamin D and redox and inflammatory status during gestation.

Methods: Three databases (PubMed/MEDLINE, Scopus, and Web of Science (WoS)) and reference list of included documents were searched for related observational studies published until 2nd October 2023. To determine the quality of the selected observational studies, the Newcastle-Ottawa Scale (NOS) was used.

Results: After a primary search of three databases, 19492records were appeared. When duplicates and irrelevant documents were removed, 14 articles were found to have eligible criteria. The design of the identified studies was cross-sectional, case-control and cohort. Evidence showed an adverse association between 25(OH)D and the biomarkers of inflammation, such as high-sensitivity C-reactive protein (hs-CRP), Interleukin-1beta (IL-1β), Interleukin-6 (IL-6), and tumor necrosis factor- alfa (TNF-α) during pregnancy. On the contrary, some studies represented that 25(OH)D positively correlated with hs-CRP in the cord blood. One study suggested a direct association between serum concentrations of 25(OH)D and Interleukin-8 (IL-8), macrophage inflammatory protein (MIP), and TNF-α levels in mothers with gestational diabetes mellitus (GDM). A case-control study showed that lower serum concentration of 25(OH)D positively correlated with total antioxidant capacity (TAC) levels in participants.

Conclusions: Evidence confirmed the supposition of the direct relationship between vitamin D levels and biomarkers with anti-inflammatory and anti-oxidative properties. However, the Existence of inconsistent evidence confirms the need for further studies in mothers with GDM and hypertensive disorders.

Prospero registration code: CRD42020202600.

Purpose: The aim of this study is to clarify the changes of peripheral CD3^-CD56⁺CD16⁺ NK cells and their correlation with Th1/Th2 immunity profiles in asthma during the phase of acute upper respiratory viral infections (AURVIs).

Methods: Peripheral venous blood and induced sputum samples were collected from 56 mild asthma patients, 49 asthma patients with AURVIs and 50 healthy subjects. Peripheral CD3^-CD56⁺CD16⁺ NK cells were monitored by flow cytometry during the course of acute viral infections. Meanwhile, the induced sputum Th2 cytokines IL-4 and IL-5, and Th1 cytokine IFN-γ were also detected by ELISA assay.

Results: The asthmatics had lower levels of peripheral CD3^-CD56⁺CD16⁺ NK cells populations as well as higher induced sputum cytokines (IL-4, IL-5 and IFN-γ) compared to healthy controls at baseline. Upon upper respiratory viral infections, peripheral CD3^-CD56⁺CD16⁺ NK cells numbers in asthma patients sharply elevated on day 3 and slowly decreased by day 14, in accordance with induced sputum IFN-γ changes. IL-4 and IL-5 levels spiked much later (day 8) and lasted until day 14. Compared with asthma alone group, the IFN-γ/IL-4 and IFN-γ/IL-5 ratios of the asthma patients with AURVIs on day 1 were higher and peaked on day 3. The changes of peripheral CD3^-CD56⁺CD16⁺ NK cells proportions positively correlated with the IFN-γ/IL-4 and IFN-γ/IL-5 ratios on day 1 to day 3 in asthma subsequent to upper respiratory viral infections.

Conclusions: Our findings showed an imbalanced Th1/Th2 immunity in airways of asthma with acute upper respiratory viral infections. Upregulated peripheral CD3^-CD56⁺CD16⁺ NK cells play a crucial role in biased Th1 immunity of airways in asthma during the acute phase of viral infections. The anti-viral Th1 immunity by targeting NK cells may be a possible therapeutic option for virus-induced asthma exacerbation.

Background: Leptospirosis is a zoonotic disease caused by Leptospira species. Variations in lipopolysaccharide (LPS) structure in Leptospira are known to be associated with the serovar diversity and antigenicity. Development of immunodiagnostics for early detection of leptospirosis based on immune responses against different pathogenic antigens as well as development of vaccines are important. Hence, this study has assessed the immune response generated against leptospiral LPS and whole antigen preparations of pathogenic and saprophytic Leptospira and specific changes in peritoneal cells was also studied to elucidate the cellular responses associated with immune response of Wistar rats.

Methods: During the study, immune response induced by two types of Leptospira antigen preparations of two selected serovars was compared. Changes in the specific peritoneal cell subpopulations following immunizations of rats were analyzed using flow cytometry.

Results: Of the two antigen preparations tested, the LPS extract induced a higher IgM immune response as opposed to the sonicated antigen preparation. Of the two serovars tested, L. interrogans serovar Pyrogenes had induced a higher IgM response compared to that by L. biflexa serovar Patoc. Considering the IgG titers, equivalent responses were observed with all four antigen preparations. Significant increases in lymphocytes were observed following immunization with LPS of both serovars. Interestingly, the B2 cell percentages increased significantly during the immunization period. Further, significant correlations were observed with both IgM and IgG responses and percentage of B2 cells in the peritoneal cavity (PC).

Conclusion: LPS extract of L. interrogans serovar Pyrogenes induced higher IgM response while the IgG response was equivalent among the four antigen preparations tested. Significant increase of B2 cell percentage in the peritoneal cavity during the immunization reflects the accumulation of B2 cells in the PC which may play considerable role in generating humoral response against Leptospira antigens.