Major depressive disorder (MDD) is a silent global health problem that can lead to suicide. MDD development is suggested to result from numerous risk factors, including genetic factors. A precise ...tool for MDD diagnosis is currently not available. Recently, inflammatory processes have been identified as being strongly involved in MDD development and the reactivation of human herpesvirus type 6 (HHV-6), upregulating cytokines such as TNF-α, which are associated with MDD. Therefore, this study aimed to determine the association of HHV-6 with genetic factors, especially TNF-α mutation, in MDD patients and their relatives compared to healthy controls. The Patient Health Questionnaire (PHQ-9) was used to evaluate MDD status, and 471 oral buccal samples were investigated for HHV-6 infection and viral copy number by qPCR. TNF-α (-308G/A) gene mutation and the cytokines TNF-α, IL-6, and IL-10 were analyzed by high-resolution melting (HRM) analysis and enzyme-linked immunosorbent assay (ELISA). Whole-exome sequencing of buccal samples was performed to analyze for genetic factors. The results showed significantly higher HHV-6 positivities and viral loads in MDD patients (15/59 (25.67%) and 14,473 ± 16,948 copies/µL DNA) and their relatives (blood relatives 17/36 (47.22%) and 8146 ± 5656 copies/µL DNA); non-blood relatives 7/16 (43.75%) and 20,721 ± 12,458 copies/µL DNA) compared to the healthy population (51/360 (14.17%) and 6303 ± 5791 copies/µL DNA). The TNF-α (-308G/A) mutation showed no significant difference. Surprisingly, 12/26 (46.15%) participants with the TNF-α (-308G/A) mutation showed HHV-6 positivities at higher rates than those with wild-type TNF-α (-308G) (70/267 (26.22%)). HHV-6-positive participants with TNF-α (-308G/A) showed higher levels of TNF-α, IL-6, and IL-10 than those of negative control. Exome analysis revealed that common mutations in immune genes were associated with depression. Therefore, this study unveiled the novel association of inflammatory gene TNF-α (-308G/A) mutations with HHV-6 reactivation, which could represent a combined risk factor for MDD. This result could induce further research on MDD development and clinical applications.
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•Pineapple kombucha has higher Blautia and Lactobacillus than original kombucha.•Functional compounds in pineapple kombucha include SCFA, acetic acid, and vitamin C.•Pineapple ...kombucha reduces the senescence of CD4 + T cells.•Pineapple kombucha reduces pro-inflammatory cytokines, such as IL-6 and IL-1β.
Kombucha is a healthy and becoming popular beverage worldwide. It is produced from tea leaves using symbiotic cultures of bacteria and yeast. Herein, we explored the use of pineapple peels and cores (by-products), as alternative ingredients for kombucha production. We examined crude pineapple kombucha (PK) for its microbial diversity, metabolites, and its impact on the cellular immune response in PBMCs older individual ex vivo. We observed a substantial shift in bacterial diversity, with higher percentages of Blautia and Lactobacillus compared with the original kombucha. This microbial variation may be attributed to the PK’s bioactive compounds. The expression of CD4+CD28null NKG2D+ senescent CD4+ T cells and pathogenic CD4+ T cells decreased, particularly in the high natural killer group 2 member D (NKG2D) expression group. This indicates the presence of bioactive substances in PK that can reduce the number of senescent CD4+ T cells. PK may be a health-promoting alternative beverage, especially for older individuals.
Melioidosis is a severe infectious disease caused by Burkholderia pseudomallei, a Gram-negative bacillus classified by the National Institute of Allergy and Infectious Diseases (NIAID) as a category ...B priority agent. Septicemia is the most common presentation of the disease with a 40% mortality rate even with appropriate treatments. Better diagnostic tests are therefore needed to improve therapeutic efficacy and survival rates.
We have used microarray technology to generate genome-wide transcriptional profiles (>48,000 transcripts) from the whole blood of patients with septicemic melioidosis (n = 32), patients with sepsis caused by other pathogens (n = 31), and uninfected controls (n = 29). Unsupervised analyses demonstrated the existence of a whole blood transcriptional signature distinguishing patients with sepsis from control subjects. The majority of changes observed were common to both septicemic melioidosis and sepsis caused by other infections, including genes related to inflammation, interferon-related genes, neutrophils, cytotoxic cells, and T-cells. Finally, class prediction analysis identified a 37 transcript candidate diagnostic signature that distinguished melioidosis from sepsis caused by other organisms with 100% accuracy in a training set. This finding was confirmed in 2 independent validation sets, which gave high prediction accuracies of 78% and 80%, respectively. This signature was significantly enriched in genes coding for products involved in the MHC class II antigen processing and presentation pathway.
Blood transcriptional patterns distinguish patients with septicemic melioidosis from patients with sepsis caused by other pathogens. Once confirmed in a large scale trial this diagnostic signature might constitute the basis of a differential diagnostic assay.
Phusang warm pond or Phusang hot spring (Thailand) has a temperature of approximately 36–38 °C and may be suitable for bacterial growth. However, data on the microbiota and effectiveness of this ...water remain obscure. Therefore, this study aimed to evaluate the characteristics of Phusang hot spring water by clarifying the microorganisms and viral pathogens present. Cytotoxicity, irritation, liposome uptake, antimicrobial and anti-inflammatory effects were evaluated. The levels of trace elements such as sodium (Na), calcium (Ca), and strontium (Sr) were confirmed. Phusang hot spring water was nontoxic to L-929 cells and HDFa cells and was nonirritating to human phototypes I to IV at 48 h. The antimicrobial effects of Phusang hot spring water on S.aureus, S. epidermidis, B. subtilis and E. coli were not detected using the agar well diffusion assay. Phusang hot spring water decreased interleukin-6 (IL-6) expression at 24 h compared with (PBS) and untreated controls, as measured using semi qRT–PCR and ELISA. Phusang hot spring water combined with curcumin-loaded liposomes exerted antiaging effects, suggesting their benefits for application in cosmetic products. The bacteriophage families Myoviridae, Siphoviridae and Podoviridae were detected, but not HPV or EBV. Trace elements such as Na and Ca were present. Therefore, the importance of this study is that Phusang hot spring water exerts anti-inflammatory effects via IL-6, is nontoxic and nonirritating, and might be used for balneotherapy or as a cosmetic ingredient under sterile conditions.
Water can contain pathogenic viruses. Many studies on RNA virus sources have shown that water can transmit them. However, there are few reports on pathogenic DNA virus transmission through water, ...such as adenovirus, which pose a widespread public health risk. Therefore, this study aimed to show waterborne viral transmission by detecting viruses in pooled human whole blood samples, tap water, and natural water from Mueang District, Phayao Province, Thailand, using a metagenomic approach. Viral prevalence in whole blood samples was measured by polymerase chain reaction (PCR) and quantitative PCR (qPCR), and environmental factors that affect viral infection were assessed. Metagenomics results showed that Epstein–Barr virus (EBV) members were among the prominent cancer-associated oncogenic DNA viruses detected in human blood and all water types similar to the EBV reference sequence (NC_007605). There were 59 out of 813 (7.26%) human whole blood samples that were positive for EBV DNA based on PCR and qPCR for the EBNA-1 and EBNA-2 genes. Water- and blood-borne human oncogenic EBV should be a concern in tap water treatment and blood transfusion in patients, respectively. Therefore, the detection of EBV in water suggests that transmission via water is possible and should be investigated further.
(Bp) is an environmental bacterial pathogen that causes potentially lethal sepsis in susceptible individuals and is considered a Category B, Tier-1 biothreat agent. As such, it is crucial to gain an ...improved understanding of protective immunity and potential vaccine candidates. The nature of immune correlates dictating why most exposed individuals in endemic regions undergo asymptomatic seroconversion while others succumb to life-threatening sepsis is largely uncharted. Bp seroreactive, immunogenic proteins have previously been identified by antigen microarray. We here set out to conduct an analysis of T-cell recognition of the Bp immunome using serodominant antigens represented in the original antigen microarray, examining immune correlates of disease in healthy seropositive individuals and those with acute disease or in convalescence. By screening a library of 739 overlapping peptides representing the sequences of 20 different Bp antigens, we aimed to define immune correlates of protection at the level of immunoprevalent T-cell epitopes. Responses to a large number of epitopes were common in healthy seropositive individuals: we found remarkably broad responsiveness to Bp epitopes, with 235 of 739 peptides recognized by ≥80% of all tested donors. The cumulative response to Bp epitopes in healthy, seropositive, donors from this endemic region were of the order of thousands of spot forming cells per million cells, making Bp recognition a significant component of the T-cell repertoire. Noteworthy among our findings, analysis revealed 10 highly immunoprevalent T-cell epitopes, able to induce Bp-specific IFNγ responses that were high in responding T-cell frequency within the repertoire, and also common across individuals with different human leukocyte antigen types. Acute melioidosis patients showed poor T-cell responses to the immunoprevalent epitopes, but acquired responsiveness following recovery from infection. Our findings suggest that a large repertoire of CD4 T cells, high in frequency and with broad coverage of antigens and epitopes, is important in controlling Bp infection. This offers an attractive potential strategy for subunit or epitope-based vaccines.
Burkholderia pseudomallei is an intracellular pathogenic bacterium that causes melioidosis in humans. On infection, neutrophils eliminate the majority of intracellular B. pseudomallei. Previous ...reports on the risk factors for melioidosis have shown that host factors, particularly age and diabetes mellitus, increase susceptibility to B. pseudomallei; however, whether these factors influence neutrophil functions in response to infection remains unknown. In this study, whole blood samples were collected from healthy Thai blood donors and co-cultured with B. pseudomallei, and phagocytic and respiratory burst functions of neutrophils were then measured by flow cytometry. The results show reduced neutrophil functions in older donors or those with poor glycemic control. Furthermore, the levels of antibody against B. pseudomallei showed a positive correlation with neutrophil functions. This study therefore indicated the importance of age, glycemic control, and antibody levels in the activity of neutrophils in melioidosis.
The use of gold nanoparticles (AuNP) has been established in nanocarriers, diagnostics, and biosensors. Access to the targeted sites of these nanomaterials could directly involve the first line of ...defense, the innate immune system. Charges of nanomaterials play a critical role in a number of aspects such as stabilization, cellular uptake, modulation, and function of cells. Interactions and modulations of the charged nanomaterials against the innate immune system may occur even at very low concentration. To understand the effects of charges on monocyte behavior, in this study, the positively and negatively charged AuNP (AuNP+ve and AuNP-ve) of the similar size and shape on cytotoxicity, recognition, cellular behavior, and function were evaluated in vitro using U937 human monocyte cells as an innate immunity model. Both types of AuNP at various concentrations (0–5 nM) exhibited low toxicity. In addition, the cellular internalization of the AuNP+ve and AuNP-ve, as determined by TEM, occurred by different mechanisms, and the internalization had no effect on cellular destruction, as implied by the low levels of %LDH. Interestingly, the AuNP+ve recognition and internalization seemingly entered cells through receptor dependence and strongly affected cellular response to express both pro-inflammatory (IL-1β) and anti-inflammatory (TGF-β) cytokines, while the AuNP-ve stimulated TNF-α expression. Nevertheless, the AuNP-treated cells maintained normal function when exposed to planktonic bacteria. Thus, these results indicated that one part of the immune system interacted with different surface-charged AuNP, suggesting appropiate immunomodulation in biomedicine.
Polymorphonuclear neutrophils (PMNs) are terminally differentiated cells that are involved in innate immune responses and form an early line of defense against pathogens. More recently, it has been ...shown that PMNs have immunosuppressive abilities on other immune cells. However, the effect of PMNs on T cell responses during bacterial infection remains to be determined. In this report, we examined the interaction of PMNs and T cells in response to infection with Burkholderia pseudomallei, the causative agent of human melioidosis. We observed that CD4(+) T cell proliferation and IFN-γ production in response to polyclonal activators is significantly inhibited by uninfected PMNs, and to a greater extent B. pseudomallei-infected PMNs. Programmed death ligand 1 (PD-L1), a known regulator of T cell activation, is increased in mRNA expression in the blood of patients and upon infection of PMNs in vitro. The increased expression of PD-L1 was correlated with the degree of T cell inhibition in individuals with type 2 diabetes, a major risk factor of melioidosis. In vitro, addition of anti-PD-L1 Abs blocked this inhibitory activity and restored proliferation of CD4(+) T cells and IFN-γ production, suggesting that PD-L1 on B. pseudomallei-infected PMNs is a regulatory molecule for the functions of T cells and may be involved in pathogenesis versus control of melioidosis.
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