Journal of Immunology Research最新文献

Introduction: Chronic kidney disease (CKD) is characterized by a decline in renal function, increased mortality, and significant impairments in the immune system and function of immune cells. These alterations are often derived by uremic toxins, which, in turn, modify the immune system's response to infections. Our research investigates the progression of Porphyromonas gingivalis (P. gingivalis) infection during CKD and its subsequent impact on kidney failure. Methods: We utilized two infectious models, a chamber model representing short-term local inflammation and alveolar bone loss that mimic chronic infection of periodontium, both in conjunction with a CKD model. Additionally, our in vitro studies employed primary macrophages, osteoclasts, and lymphocytes to characterize the immune responses to P. gingivalis and pathogen-associated molecular patterns (PAMPs) in the presence of uremic toxins. Results and Conclusion: Our findings demonstrate that uremic toxins, such as indoxyl sulfate (IS), alter responses of macrophages and lymphocytes to P. gingivalis. In vivo, CKD significantly enhanced P. gingivalis survival and infection-induced alveolar bone loss. The increased distribution of pathogen within peripheral tissues was associated with altered inflammatory responses, indicating that CKD promotes infection. Moreover, P. gingivalis-infected mice exhibited a marked increase in renal inflammation, suggesting that the relationship between uremia and infection is bidirectional, with infection exacerbating kidney dysfunction. Furthermore, we observed that infected CKD mice exhibit decreased serum immunoglobulin G (IgG) levels compared to infected mice without CKD, implying that uremia is associated with immune dysfunction characterized by immunodepression and impaired B lymphocyte function.

Brucella canis is a Gram-negative bacterium that causes canine brucellosis, a zoonotic disease with serious implications for public health and the global economy. Currently, there is no effective preventive vaccine for B. canis. Control measures include diagnostic testing, isolation, and euthanasia of infected animals. However, these measures face significant limitations, such as diagnostic challenges, ethical concerns, and limited success in preventing transmission. Epidemiologically, canine brucellosis exhibits seroprevalence rates ranging from less than 1% to over 15%, with higher rates reported in stray dogs and regions of low socioeconomic development. This study employed a reverse vaccinology approach to design and characterize a multiepitope vaccine candidate against B. canis, aiming to prevent infection caused by this pathogen. A comprehensive in silico analysis of the complete B. canis proteome was conducted to identify proteins with potential as vaccine targets. Predicted epitopes for B and T cells were analyzed, and those with the highest capacity to elicit a robust immune response were selected. These proteins were classified as plasma membrane proteins, outer membrane proteins (OMPs), or proteins with similarity to virulence factors. Selection criteria emphasized their essential roles in bacterial function, lack of homology with proteins from dogs or mice, and presence of fewer than two transmembrane domains. From this process, four candidate proteins were identified. Epitopes for B and T cells within these proteins were predicted and analyzed, selecting the most immunogenic sequences. The overlap between B- and T-cell epitopes narrowed the selection to six final epitopes. These selected epitopes were then assembled into a multiepitope vaccine construct using flexible linkers to ensure structural integrity and molecular adjuvants to enhance immunogenicity. The physicochemical properties, antigenicity, and toxicity of the designed vaccine were evaluated. Additionally, the secondary and tertiary structure of the vaccine was predicted and refined, followed by a molecular interaction analysis with the Toll-like receptor 4 (TLR4) receptor. The designed vaccine proved to be highly antigenic, nonallergenic, and nontoxic. Validation of its secondary and tertiary structures, along with molecular docking analysis, revealed a high binding affinity to the TLR4 receptor. Molecular dynamics simulations and normal mode analysis further confirmed the vaccine's structural stability and binding capacity. A multiepitope vaccine candidate against B. canis was successfully designed and characterized using a reverse vaccinology approach. This vaccine construct is expected to induce robust humoral and cellular immune responses, potentially conferring protective immunity against B. canis. The results of this study are promising; however, in vitro and in vivo tests are necessary to validate the vaccine's protec

Colorectal cancer (CRC) stands as one of the tumors with globally high incidence and mortality rates. In recent years, researchers have extensively explored the role of the tumor immune microenvironment (TME) in CRC, highlighting the crucial influence of immune cell populations in driving tumor progression and shaping therapeutic outcomes. The TME encompasses an array of cellular and noncellular constituents, spanning tumor cells, immune cells, myeloid cells, and tumor-associated fibroblasts, among others. However, the cellular composition within the TME is highly dynamic, evolving throughout different stages of tumor progression. These shifts in cell subpopulation proportions lead to a gradual transition in the immune response, shifting from an early antitumor growth to a late-stage environment that supports tumor survival. Therefore, it is crucial to further investigate and understand the complex interactions among the various cell populations within the TME. In this review, we explore the key cellular components of varying origins, subpopulations with shared origins, and noncellular elements within the CRC TME, examining their interconnections and critical considerations for developing personalized and precise immunotherapy strategies.

Antiphospholipid syndrome (APS) is frequently coexisting with systemic lupus erythematosus (SLE) and the knowledge on its genetic background is essential. The objective of this work was to assess distribution of human leukocyte antigen (HLA)-DRB1 alleles in patients with APS with or without SLE in the context of Polish population data. The study was performed in a group of 112 patients with APS and healthy subjects to assess the distribution of HLA-DRB1 alleles in patients with APS and their association with clinical characteristics of patients with APS-antiphospholipid antibodies (aPLs) presence and disease activity/damage indexes. The distribution of HLA-DRB1 alleles showed significant differences between patients with APS and healthy subjects. Allelic variant HLA-DRB1⁣ ^∗ 1.15 was identified as risk alleles for APS observed in patients with APS (odds ratio (OR): 2.06 (1.27, 3.23), p=0, 004), while HLA-DRB1⁣ ^∗ 1.07 showed significant protective association (OR: 0.37 (0.14-0.76), p=0, 006). In subgroup of patients with coexisting SLE allelic variants above were not identified as risk or protective, while protective association was described for HLA-DRB1⁣ ^∗ 01, but not for patients in primary APS group. Presence of antibodies anti-β ₂-glycoprotein-I (aβ ₂GPI) IgA and against domain 1, anti-phosphatidylserine/prothrombin (aPS/PT) and anticardiolipin antibody (aCL) IgA all the antibodies which were negatively associated with HLA-DRB1⁣ ^∗ 15.01 carriers, what was reported for the first time may be suitable in discussion about value of these antibodies in practice and scientific research. This study clearly shows that primary APS has a distinct HLA-DRB1 associations as compared with SLE with a strong positive association with HLA-DRB1⁣ ^∗ 15.01 allele and a protective association with HLA-DRB1⁣ ^∗ 07.01.

Malaria is a parasitic infectious disease considered a public health problem. Acute respiratory distress syndrome (ARDS) is a complication in malaria-infected individuals with a high mortality rate (80% to 100%) and can occur before, during, or after antimalarial drug treatment. Although inflammation and epithelial/endothelial injury pathways have been determined through these studies, specific circulating malaria-associated ARDS markers have not yet been established. We applied a quantitative mass spectrometry (MS)-based proteomic approach to identify altered molecular pathways in a mouse model of malaria-associated ARDS. Acute-phase response (APR) proteins were regulated in the ARDS group, suggesting their potential involvement in the development of the syndrome. They may serve as biomarkers when analyzed alongside other proteins that require further investigation. Additionally, the regulation of APR proteins in the ARDS group provides valuable insights into the pathophysiology of ARDS, contributing to a better understanding of the syndrome.

Introduction: Tumor-infiltrating B cells (TILBs) are an important part of the immune response during tumor regulation. However, the significance of B cells in immunotherapy has not been fully determined. Methods: In this study, highly expressed genes in B cells were obtained by comparing the gene expression in B cells with that in other immune cells and were named TILB-mRNAs. Among them, those genes expressed in patients with head and neck squamous cell carcinoma (HNSCC) identified in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) atlas were employed to screen for genes associated with HNSCC prognosis using univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) regression analysis, and a TILB-related signature was constructed to predict patient prognostic risk using multivariate Cox regression analyses. Results: The constructed TILB-related signature, which comprised seven mRNAs (ZNF439, KMO, KDM5D, IFT57, HDAC9, GSAP, and CCR7), was verified to have a good ability to predict the prognosis of patients with HNSCC using three independent validation datasets from GEO, and the predictive ability was not affected by other factors. The signature reflected the state of immune cell infiltration in tumor tissue, especially B cells, patients with higher risk scores (RSs) had fewer infiltrating immune cells in their tumors, especially B cells. The gene expression of the TILB-related signature was also verified in TILBs from HNSCC using single-cell analysis, revealing that TILB-related marker genes were differentially expressed in different GB cell subsets. Discussion: This study provides risk assessment and outcome prediction for patients with HNSCC and provides potential targets for immunotherapy of HNSCC.

The objective of this study is to measure lymphocyte responses to metal antigens using MELISA (memory lymphocyte immunostimulation assay) test-modified lymphocyte transformation test (mLTT) and to evaluate metal sensitization in patients with and without the need of prosthetic surgery. This study is a case-control retrospective survey. We retrospectively analyzed all patients from 2013 to 2018 who were referred to the Institute of Dental Medicine, General University Hospital in Prague, and First Faculty of Medicine, Charles University, Prague, either following joint prosthesis-related complications or as a preoperative evaluation concerning metal hypersensitivity. For the control group, we selected healthy adults from our database. A group of 127 patients aged 25-81 years was chosen, 92 of which were female and 35 were male. The patients completed a special questionnaire aimed at information regarding their health status and history of metal exposure. After clinical examination, their peripheral blood samples were taken to perform mLTT. mLTT provided quantitative lymphocyte proliferation measurement, where a stimulation index of >2 indicated metal sensitivity. For statistical analysis, the Fisher's exact test, χ² test, McNemar's exact test Student's paired t-test were used. By comparison of the study group and control group mLTT results, it can be stated that patients of the study group showed a higher level of lymphocyte reactivity to most of the tested metal antigens (Ag [silver], Cu [copper], Fe [iron], Mo [molybdenum], Pd [palladium], Pt [platinum], Ti [titanium], and Zn [zinc]) and an elevated incidence of metal hypersensitivity to Hg (mercury), Al (aluminum), Au (gold), Co (cobalt), Cr (chromium), Ni (nickel), and Sn (tin). The evaluation of the data obtained from patients in this study confirmed a significant clinical benefit of mLTT in diagnostics of metal hypersensitivity. Our study has revealed that the patients with the need of prosthetic surgery exhibited an elevated lymphocyte response to metal antigens. This result supports a metal-specific adaptive immune response and suggests involvement of metal exposure as a trigger for their health problems. This knowledge could be helpful in effectively enhancing the treatment of patients with need of orthopedic joint prosthesis.

Infections of central nervous system (ICNSs) are inflammatory diseases caused by infectious agents that can infiltrate the brain and spinal cord through various routes, including the bloodstream, peripheral nerves, or cranial nerves. Exosomes are found in plasma and have the capacity to cross the blood-brain barrier (BBB). Exosome constituents, including lipids, proteins, DNA, and RNA, change significantly over time and are correlated with the course of disease. Circular RNA (circRNA) has become a potential biomarker for various diseases, such as ICNSs. This study explores the diagnostic potential of circRNAs derived from brain-derived exosomes in ICNSs. Our research shows that the brain-derived exosomes from patients with CNS illnesses have different patterns of circRNA expression than those from healthy controls. Plasma samples from patients with bacterial ICNSs show significantly elevated levels of hsa_circ__0020840 and hsa_circ_0116108. In contrast, higher expression levels of hsa_circ_0056947 and hsa_circ_0021531 are observed in plasma samples from individuals with viral ICNSs compared to healthy subjects. These observations suggest their potential utility as sensitive and specific biomarkers for these diseases. Moreover, the capacity of circRNAs to be encapsulated within exosomes and released into circulation offers a noninvasive approach for diagnosing ICNSs. These findings highlight the promise of utilizing brain-derived exosomal circRNAs as novel diagnostic markers for ICNSs, which may have implications for improving patient outcomes and disease management.

In response to various stressors, cells can enter a state called cellular senescence which is characterized by irreversible cell cycle arrest and a senescence-associated secretory phenotype (SASP). The progressive accumulation of senescent glial cells in the central nervous system (CNS) with aging suggests a potential role for senescence as driver of aging and inflammation in the brain. As the main immune cell population residing in the CNS, microglia are thought to play a pivotal role in the progression of age-associated neuroinflammation. Furthermore, due to their slow turnover, microglia are highly susceptible to undergoing cellular senescence. However, current understanding of age-related changes in microglia and their impact on brain aging is limited. Due to the challenge in accessing human primary microglia and the lack of models to adequately recapitulate aging, this knowledge is predominantly limited to rodent studies. Here, we chemically induced senescence in a human immortalized microglia cell line with a cocktail of senescence-inducing molecules. We demonstrate that chemically induced senescent microglia adopt a proinflammatory phenotype, have reduced phagocytic activity, and impaired calcium activity. Our results show that chemically induced senescence can mimic features of cellular aging and can provide insight into the impact of aging and cellular senescence on human microglia.

Nucleated red blood cells (NRBCs) are precursors of red blood cells (RBCs), but also possess variety of immunomodulatory effects. However, among the three types of NRBCs, the immunological effects of human CD45- NRBCs remain largely unknown. We have previously shown that cord blood-derived CD45- NRBCs and adult peripheral blood-derived monocytes cocultured in a lipopolysaccharide (LPS)-stimulated indirect coculture system that avoided cell-to-cell contact, increase IL-10 and decrease TNF-α secretion, suggesting an immunosuppressive function of CD45- NRBCs via an unknown soluble factor. The peripheral blood of fetuses and neonates has abundant NRBCs and is physiologically polycythemic, which may lead to the peripheral accumulation of toxic plasma-free hemoglobin. Plasma-free hemoglobin binds to haptoglobin, forming a haptoglobin-hemoglobin complex, which is processed within monocytes via the CD163- heme oxygenase 1 (HO-1) axis and secretes IL-10. Therefore, we hypothesized that NRBCs secrete haptoglobin and induce the immunosuppressive function of monocytes by activating the CD163-HO-1 axis. We found that immunosuppressive response decreased when the coculture medium was supplemented with an anti-CD163 blocking antibody or the HO-1 inhibitor zinc protoporphyrin IX (ZnPP-IX). Haptoglobin levels in the culture medium containing NRBCs were high and expressed the haptoglobin gene. Thus, CD45- NRBCs secreted haptoglobin and activated the immunosuppressive function of monocytes.