BMC Immunology最新文献

The Mokola Virus belongs to the family Rhabdoviridae and is genotype 3 of the Lyssavirus genera. A small number of cases of animal and human encephalomyelitis, mainly scattered over sub-Saharan Africa, have been linked to the Mokola Virus (MOKV). Currently there is no vaccine to protect against MOKV infection in people or animals. It has been proven that rabies vaccination does not confer immunity against MOKV infection, even though MOKV and the rabies virus are related. Using immunoinformatics approaches, this study designed an mRNA vaccine that can protect against all the five glycoproteins of the Mokola virus. NCBI was used to obtain the viral sequences, which were then screened for antigenicity, allergenicity, toxicity, B-cell epitopes, CD8 + T lymphocytes (CTL), and CD4 + T lymphocytes (HTL). These epitopes were used in the construction of the vaccine. Some extra co-translational residues were added to the mRNA vaccine construct. Its molecular weight is 129.19083 kDa, and its estimated pI is 8.58. It interacts rather steadily and with limited deformability with TLR 3, among other human innate immune receptors. Overall, the results show that the produced candidate vaccine is non-allergen, non-toxic, and can elicit T-cell and B-cell immune responses. These findings can further be subjected to in-vivo and in-vitro techniques for validation.

Objectives: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Four types of RNA modification writers (m6A, m1A, A-I editing, and APA) are widely involved in tumorigenesis and the TME. We aimed to comprehensively explore the role of the four RNA modification writers in the progression and immune microenvironment of HNSCC.

Materials and methods: We first obtained transcription profile data and transcriptional variation of the four types of RNA modification writers from The Cancer Genome Atlas (TCGA) database. HNSCC patients in TCGA dataset were divided into different clusters based on the four types of RNA modification writers. Univariate Cox and Least absolute shrinkage and selection operator (LASSO) analyses were performed to conduct a Writer-score scoring system, which was successfully verified in the GSE65858 dataset and our clinical sample dataset. Finally, we evaluated the relationship between different RNA modification clusters (Writer-score) and immunological characteristics of HNSCC.

Results: Two different RNA modification clusters (A and B) were obtained. These RNA modification clusters (Writer-score) were strongly associated with immunological characteristics (immunomodulators, cancer immunity cycles, infiltrating immune cells (TIICs), inhibitory immune checkpoints, and T cell inflamed score (TIS)) of HNSCC.

Conclusions: This study identified two different RNA modification clusters and explored the potential relationship between RNA modification clusters (Writer-score) and immunological characteristics, offering a new theoretical basis for precision immunotherapy in patients with HNSCC.

Aims: We aimed to investigate the anxiolytic effect of darbepoetin alpha (DEPO), an erythropoietin derivative, in a neuroinflammation model regarding different behaviors and biological pathways.

Methods: Forty adult male Wistar albino rats were divided into four groups (control, LPS, DEPO, and DEPO + LPS). The rats were treated with 5 µg /kg DEPO once a week for four weeks, after which neuroinflammation was induced with 2 mg/kg lipopolysaccharide (LPS). The elevated plus maze, open-field, and light‒dark box tests were conducted to assess anxiety levels. Harderian gland secretions were scored via observation. Tumor necrosis factor alpha (TNF-α), Interleukin-1-beta (IL-1β), brain-derived growth factor (BDNF), serotonin, cortisol, total antioxidant/oxidant (TAS/TOS), and total/free thiol levels were measured in the prefrontal cortex, striatum, and serum.

Results: DEPO had a potent anxiolytic effect on both DEPO and DEPO + LPS groups. Compared to the control group, DEPO administration caused an increase in serotonin and BDNF levels and decreased basal cortisol and TNF-α levels in naive rats. IL-1β did not alter after DEPO administration in naive rats. Prophylactic DEPO treatment remarkably downregulated cortisol, IL-1β, and TNF-α in the DEPO + LPS group. In addition, prophylactic DEPO administration significantly attenuated the decrease in serotonin and BDNF levels in the DEPO + LPS group. Furthermore, DEPO ameliorated excessive harderian gland secretion in the DEPO + LPS group. Compared with those in the control group, the free thiol content in the serum increased after DEPO administration. No similar effect was seen in the DEPO + LPS group receiving prophylactic DEPO. TAS showed no difference among all experimental groups. DEPO administration increased TOS and OSI in the serum and prefrontal cortex but not in the striatum. This effect was not seen in the DEPO + LPS group.

Conclusion: Darbepoetin alpha had an anxiolytic effect on many physiological mechanisms in a neuroinflammation model and naive rats.

Background: In the current study, we evaluated whether atopic dermatitis (AD) affects the entire body rather than being limited to skin barrier damage and inflammation. We hypothesized that medium-term exposure of distant organs to systemic inflammatory cytokines in sub-chronic inflammatory skin diseases has detrimental effects on distant tissues.

Results: Our findings demonstrated the dysregulation of genes and pathways associated with inflammation and the skin barrier, as well as genes and pathways involved in muscle development that respond to chemicals or stress in muscle tissues, all of which were reversed by hydrocortisone (Hc) administration. The expression of Ces1d showed significant differences during disease onset and after treatment in both skin and skeletal muscle, suggesting that Ces1d is likely responsible for the alleviation of subchronic AD.

Conclusions: Using NC/Nga mice with AD-like symptoms, we compared the transcriptomes of the skeletal muscle (a tissue that is relatively distant from the skin) with those of the skin (the lesion induction site) before and after disease induction, after which Hc was administered. Although further study is needed to better understand the effects of Ces1d on AD, skeletal muscle was associated with AD pathogenesis, and AD-like symptoms appeared to affect the body in a systemic manner. Given the importance of evidence-based medicine and the development of precision medicine, our findings provide insights into the mechanisms of AD onset and progression.

Background: To introduce the serum total kappa/lambda ratio (K/L) in humoral immunity testing reports to improve the detection rate of M-proteinemia.

Methods: 156 M protein-positive and 5464 M protein-negative samples confirmed by serum immunofixation electrophoresis(sIFE) were accumulated from January 2021 to December 2023 in the First Affiliated Hospital of Soochow University and the contents of immunoglobulins (IgG, IgA, IgM, kappa and lambda) were tested by Beckman IMMAGE800. All the samples were divided into two groups by time: the modeling group and the validation group. The K/L values in the modeling group were analyzed by SPSS 27.0 to get the receiver operating characteristic curve (ROC). Furthermore, a more in-depth analysis was conducted to verify the reliability of the optimal cutoff values in the validation group. In addition, the levels of immunoglobulins of another group including 106 patients with definite diagnosis of monoclonal gammopathy ranging from January 2021 to June 2024 were traced back to improve the diagnostic efficiency.

Results: The optimal cutoff values of K/L were 2.31 and 1.43 corresponding to K-type and L-type M-proteinemia respectively by ROC analysis. The sensitivity and specificity were validated as 76.14% and 77.42%. False positives were mainly found in samples with systemic sclerosis (36.84%), hypohepatia (28.71%) and sicca syndrome (27.27%). While false negatives were mainly found in IgA monoclonal gammopathy (38.39%) and IgM monoclonal gammopathy (28.57%). Combining with the detection rules of IgG, IgA and IgM, the sensitivities for the diagnosis of immunoglobulin light chain amyloidosis(AL) and monoclonal gammopathy of undetermined significance(MGUS) can be increased to 83.33% and 85%.

Conclusions: K/L > 2.31 and K/L < 1.43 can be used as warning values for M-proteinemia. In addition, the content of the heavy chain in IgA- or IgM-type M-proteinemia may be considered to improve the detection rate.

Background: Despite the development of various antiviral drugs, most of them are not effective in the treatment of coronavirus disease 2019 (COVID-19) as a hyperinflammatory disorder. Chemokine (C-C motif) ligand 2 (CCL2) is one of the critical CC chemokines involved in the pathogenesis and severity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. This study aimed to investigate the expression of CCL2 and CC chemokine receptor 2 (CCR2) in COVID-19 patients.

Methods: Peripheral blood samples were collected from 60 confirmed COVID-19 patients and 60 age-matched healthy subjects. The ages of the subjects were categorized as follows: up to 20 years, 20 to 40 years, 40 to 60 years, and more than 60 years. CCL2 serum levels were measured using the enzyme-linked immunosorbent assay (ELISA). CCR2 gene expression in peripheral blood mononuclear cells (PBMCs) was measured employing real-time polymerase chain reaction (PCR).

Results: In all age groups, CCL2 serum levels were significantly elevated in patients compared to healthy controls (P < 0.0001). CCL2 levels were higher in severe patients than in moderate patients. Moreover, CCR2 expression by PBMCs was higher in patients compared to control subjects. However, a significant difference between patients and controls over 60 years of age was identified (P = 0.0353). There was no significant difference in CCR2 expression between moderate and severe COVID-19 patients.

Conclusions: Taken together, the findings demonstrate that CCL2 and CCR2 are upregulated in COVID-19 patients at protein and mRNA levels, respectively. Therefore, the CCL2/CCR2 axis may be a potential therapeutic target in order to improve patient outcomes.

Immune thrombocytopenia (ITP) is a prevalent hemorrhage condition that causes notable immune-related abnormalities. Recently discovered data has shown that the intestinal flora plays a crucial role in maintaining a balanced immune system. Furthermore, an imbalance in gut flora has the potential to increase the possibility of developing ITP. Moreover, some studies reported a strong link between inflammatory bowel disease (IBD) and ITP. In this review, we described the significance of gut immunity in ITP. In addition, we explored the associations between gut flora and ITP as well as IBD and ITP. Finally, we examined the effectiveness of existing therapies that regulate gut homeostasis and their impact on the prognosis of patients with ITP.

Background: Porphyromonase gingivalis (P. gingivalis) is a type of bacteria that causes periodontitis, which is strongly correlated with systemic diseases such as diabetes. However, the effect of hyperglycemia on periodontitis are unclear. The present study examined the effects of high glucose levels on the response to P. gingivalis infection.

Results: The expression of P. gingivalis-induced interleukin-1β (IL-1β) and inflammasomes increased as the glucose concentration increased. High glucose conditions suppressed P. gingivalis-induced autophagy in human acute monocytic leukemia cell line (THP-1) macrophages. Zingerone increased autophagy and alleviated P. gingivalis-induced inflammatory response in THP-1 macrophages under high glucose conditions. In addition, P. gingivalis- induced inflammation in bone marrow-derived macrophages of diabetic mice was higher than in wild-type mice, but a zingerone treatment decreased the levels. Alveolar bone loss due to a P. gingivalis infection was significantly higher in diabetic mice than in wild-type mice.

Conclusions: High-glucose conditions aggravated the inflammatory response to P. gingivalis infection by suppressing of autophagy, suggesting that autophagy induction could potentially to treat periodontitis in diabetes. Zingerone has potential use as a treatment for periodontal inflammation induced by P. gingivalis in diabetes patients.

We previously demonstrated that the overall number of regulatory T (Treg) cells decrease proportionately with helper CD4⁺ T cells and their frequencies increase in antiretroviral therapy (ART)-naive human immunodeficiency virus type-1 (HIV-1) infected individuals. The question now is whether the discrepancies in Treg cell numbers and frequencies are synonymous to an impairment of their functions. To address this, we purified Treg cells and assessed their ability to modulate autologous monocytes functions. We observed that Treg cells were able to down modulate autologous monocytes activation as well as interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) production during stimulation with polyinosinic-polycytidylic acid stabilized with poly-L-lysine and carboxymethylcellulose (poly-ICLC). This activity of Treg cells has been shown to be influenced by immunocompetence including but not limited to helper CD4⁺ T cell counts, in individuals with HIV-1 infection. Compared to immunosuppressed participants (CD4 < 500 cells/µL), immunocompetent participants (CD4 ≥ 500 cells/µL) showed significantly higher levels of transforming growth factor beta (TGF-β) and IL-10 (p < 0.001 and p < 0.05, respectively), key cytokines used by Treg cells to exert their immunosuppressive functions. Our findings suggest the contribution of both TGF-β and IL-10 in the suppressive activity of Treg cells.