SARS-CoV-2, a positive-strand RNA virus, utilizes both genomic replication and subgenomic mRNA transcription. Whole genome sequencing (WGS) from clinical samples can estimate viral gene expression levels. WGS was conducted on 529 SARS-CoV-2 positive clinical samples from Assam and northeastern India to track viral emergence and assess gene expression patterns.
View Article and Find Full Text PDFCytokines mediate T-helper (TH) responses that are crucial for determining the course of infection and disease. The expression of cytokines is regulated by transcription factors (TFs). Here we present the frequencies of single nucleotide polymorphisms (SNPs) in cytokine and TF genes in a Zimbabwean population, and further relate SNPs to susceptibility to schistosomiasis and cytokine levels.
View Article and Find Full Text PDFObjectives: IFNγ-release assays (IGRAs) used for diagnosis of Mycobacterium (M.) tuberculosis infection have limited sensitivity. Alternative cytokines and M.
View Article and Find Full Text PDFSOCS3 is a crucial feedback inhibitor of several cytokine pathways with potential regulatory functions during T cell receptor activation. A role of SOCS3 in IL-7-dependent homeostatic mechanisms has been assumed but the underlying mechanisms remain unclear. We investigated the role of SOCS3 in IL-7 receptor α-chain (IL-7Rα) expression and IL-7 effects on activated human CD4 T cells.
View Article and Find Full Text PDFIFN-γ release assays (IGRAs) have suboptimal sensitivity for detection of Mycobacterium tuberculosis (Mtb) infection and cannot discriminate between tuberculosis (TB) patients and healthy -potentially Mtb infected- contacts (HCs). In a case-control study, we determined T-cell phenotypes of IGRAs in TB patients (n = 20) and HCs (n = 20) from Ghana. CD27 expression of T-cells was significantly lower in TB patients as compared to HCs independent from Mtb-specificity.
View Article and Find Full Text PDFIFN-γ release assays [e.g., QuantiFERON (QFT)] are widely used for diagnosis of () infection.
View Article and Find Full Text PDFTreating is challenged by the low efficacy of registered antihelminthics. endobacteria provide an alternative treatment target because depletion results in amicrofilaremia in filarial infections with and infections. This open-label, randomized study sought to confirm that i) are present in in Ghana and ii) doxycycline treatment will deplete and cause a slow, sustained decline in microfilariae (MF).
View Article and Find Full Text PDFT-cells critically contribute to protection against Mycobacterium tuberculosis infection, and impaired T-cell responses can lead to disease progression. Pro-inflammatory and immunosuppressive cytokines affect T-cells, and fine-tuned regulation of cytokine signaling via the Jak/STAT signaling pathways is crucial for appropriate T-cell function. Constitutive STAT3 phosphorylation as a consequence of aberrant cytokine signaling has been described to occur in pathognomonic T-cell responses in inflammatory and autoimmune diseases.
View Article and Find Full Text PDFFunctional interleukin-7 receptor α-chain (IL-7Rα) genetic variants, which affect alternative splicing and expression of the soluble IL-7Rα, are associated with susceptibility to autoimmunity. We previously described aberrant IL-7Rα expression and impaired IL-7-mediated T-cell functions in tuberculosis patients. In the present study, we investigated a possible role of IL7RA gene variants.
View Article and Find Full Text PDFPLoS Negl Trop Dis
January 2018
The filarial nematode Mansonella perstans is endemic throughout Africa, northern South America and the Caribbean. Interestingly, M. perstans-infected individuals present no distinct clinical picture associated with certain pathology.
View Article and Find Full Text PDFT-cell proliferation and generation of protective memory during chronic infections depend on Interleukin-7 (IL-7) availability and receptivity. Regulation of IL-7 receptor (IL-7R) expression and signalling are key for IL-7-modulated T-cell functions. Aberrant expression of soluble (s) and membrane-associated (m) IL-7R molecules is associated with development of autoimmunity and immune failure in acquired immune deficiency syndrome (AIDS) patients.
View Article and Find Full Text PDFIFN-γ release assays (IGRAs) often present false-negative or indeterminate results in children with tuberculosis. HIV co-infection may contribute to decreased sensitivity of IGRAs by impairing T-cell IFN-γ expression. Measurement of alternative cytokines in QuantiFERON (QFT) supernatants can circumvent the IFN-γ-dependency and may improve QFT sensitivity.
View Article and Find Full Text PDFBackground: Buruli ulcer disease (BUD), caused by Mycobacterium (M.) ulcerans, is the third most common mycobacterial disease after tuberculosis and leprosy. BUD causes necrotic skin lesions and is a significant problem for health care in the affected countries.
View Article and Find Full Text PDFMacrophages are natural host cells for pathogenic mycobacteria, like Mycobacterium tuberculosis (M.tb). Immune surveillance by T cells and interaction with M.
View Article and Find Full Text PDFBackground: Mansonellosis was first reported in Ghana by Awadzi in the 1990s. Co-infections of Mansonella perstans have also been reported in a small cohort of patients with Buruli ulcer and their contacts. However, no study has assessed the exact prevalence of the disease in a larger study population.
View Article and Find Full Text PDFSchistosomiasis is a major public health problem in Africa. However, it is only recently that its burden has become recognised as a significant component impacting on the health and development of preschool-aged children. A longitudinal study was conducted in Zimbabwean children to determine the effect of single praziquantel treatment on Schistosoma haematobium-related morbidity markers: microhaematuria, proteinuria, and albuminuria.
View Article and Find Full Text PDFBackground: Several infectious diseases and therapeutic interventions cause gut microbe dysbiosis and associated pathology. We characterised the gut microbiome of children exposed to the helminth Schistosoma haematobium pre- and post-treatment with the drug praziquantel (PZQ), with the aim to compare the gut microbiome structure (abundance and diversity) in schistosome infected vs. uninfected children.
View Article and Find Full Text PDFSchistosoma haematobium affects more than 100 million people throughout Africa and is the causative agent of urogenital schistosomiasis. The parasite is strongly associated with urothelial cancer in infected individuals and as such is designated a group I carcinogen by the International Agency for Research on Cancer. Using a protein microarray containing schistosome proteins, we sought to identify antigens that were the targets of protective IgG1 immune responses in S.
View Article and Find Full Text PDFBackground: Group 2 Innate lymphoid cells (ILC2s) are innate cells that produce the TH2 cytokines IL-5 and IL-13. The importance of these cells has recently been demonstrated in experimental models of parasitic diseases but there is a paucity of data on ILC2s in the context of human parasitic infections and in particular of the blood dwelling parasite Schistosoma haematobium.
Methodology/principal Findings: In this case-control study human peripheral blood ILC2s were analysed in relation to infection with the helminth parasite Schistosoma haematobium.
Background: Several studies have been conducted quantifying the impact of schistosome infections on health and development in school-aged children. In contrast, relatively little is known about morbidity levels in preschool-aged children (≤ 5 years) who have been neglected in terms of schistosome research and control. The aim of this study was to compare the utility of available point-of-care (POC) morbidity diagnostic tools in preschool versus primary school-aged children (6-10 years) and determine markers which can be used in the field to identify and quantify Schistosoma haematobium-related morbidity.
View Article and Find Full Text PDFThe CD3ζ forms part of the T cell receptor (TCR) where it plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways leading to T cell effector functions. Down regulation of CD3ζ leads to impairment of immune responses including reduced cell proliferation and cytokine production. In experimental models, helminth parasites have been shown to modulate immune responses directed against them and unrelated antigens, so called bystander antigens, but there is a lack of studies validating these observations in humans.
View Article and Find Full Text PDFHuman IgG1 antibody responses are associated with protection against Schistosoma haematobium infection and are now a target for schistosome vaccine development. This study aimed to investigate the relationship between total IgG and the IgG subclasses and the monocyte IgG receptor, known as FcγRIIIa or CD16, in schistosome exposed people. Systemic levels of schistosome-specific anti-adult worm total IgG and IgG subclass titres were measured by ELISA in 100 individuals from an S.
View Article and Find Full Text PDFHuman gastrointestinal bacteria often share their environment with parasitic worms, allowing physical and physiological interaction between the two groups. Such associations have the potential to affect host health as well as the bacterial and helminth populations. Although still in its early stages, research on the interaction between the microbiome and parasitic helminths in humans offers the potential to improve health by manipulating the microbiome.
View Article and Find Full Text PDFBackground: Improved helminth control is required to alleviate the global burden of schistosomiasis and schistosome-associated pathologies. Current control efforts rely on the anti-helminthic drug praziquantel (PZQ), which enhances immune responses to crude schistosome antigens but does not prevent re-infection. An anti-schistosome vaccine based on Schistosoma haematobium glutathione-S-transferase (GST) is currently in Phase III clinical trials, but little is known about the immune responses directed against this antigen in humans naturally exposed to schistosomes or how these responses change following PZQ treatment.
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