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Introduction
Current institution
Publications
Publications (45)
Immunopathology of human tuberculosis (TB) in a subgroup of patients is characterized by aberrantly high concentrations of inflammatory cytokines, for example Interleukin (IL)-6. Concomitant (co-)infections by parasites can affect host immunity, but the impact on immunopathology in TB patients is poorly defined. Here we characterized a group of pat...
BCG vaccination affects other diseases beyond tuberculosis by unknown—potentially immunomodulatory—mechanisms. Recent studies have shown that BCG vaccination administered during overt type 1 diabetes (T1D) improved glycemic control and affected immune and metabolic parameters. Here, we comprehensively characterized Ghanaian T1D patients with or wit...
Background
Culicoides, also known as biting midges, carry pathogens which include Mansonella perstans. Mansonella perstans is a nematode parasite implicated in a number of disease outcomes. Even though a high prevalence of about 75% M. perstans infection has been recorded in some communities in the middle belt of Ghana, and a wide diversity of Culi...
Host immune response is key for protection in tuberculosis, but the causative agent, Mycobacterium (M.) tuberculosis, manages to survive despite immune surveillance. Key mechanisms of immune protection have been identified, but the role of immunopathology in the peripheral blood of tuberculosis patients remains unclear. Tuberculosis immunopathology...
Impaired T-cell responses to mitogens and high T-cell activation marker (TAM) expression on Mycobacterium tuberculosis –specific T-cells characterize immunopathology in patients with tuberculosis (TB). In a study of patients with TB ( n = 60) and asymptomatic contacts (controls, n = 37), we found that TB patients had higher CD38 ⁺ T-cell proportion...
Immunopathology in human tuberculosis affects T-cell phenotype and functions. Previous studies identified impaired T-cell sensitivity to Interleukin (IL)-7 accompanied by lower IL-7 receptor α-chain (IL-7Rα) expression in patients with acute tuberculosis. In the present study, we characterized affected T-cell subsets and determined the influence of...
Background
Buruli ulcer disease (BUD) caused by Mycobacterium (M.) ulcerans is characterized by necrotic skin lesions. As for other mycobacterial infections, e.g., tuberculosis, the immune response is important for host protection. B-cells may play a role in antimycobacterial immunity but studies characterizing the B-cell repertoire and memory gene...
Introduction:
Immediate fixation of smears in 95% alcohol for Pap-staining is commonly used for cytopathological diagnosis of cancers and other diseases. Few research has investigated the comparative outcomes of alcohol wet-fixation and rehydration of air-dried smears, indicating that rehydration of air-dried smears are viable alternative to wet-f...
Monocyte-derived macrophages contribute centrally to immune protection in Mycobacterium tuberculosis infection and changes in monocyte phenotype characterize immunopathology in tuberculosis patients. Recent studies highlighted an important role of the plasma milieu in tuberculosis immunopathology. Here, we investigated monocyte pathology in patient...
Mycobacterium (M.) bovis BCG vaccination is recommended for healthy babies after birth in several countries with a high prevalence of tuberculosis, including Ghana. Previous studies showed that BCG vaccination prevents individuals from developing severe clinical manifestations of tuberculosis, but BCG vaccination effects on the induction of IFN-γ a...
Purpose
Human tuberculosis is characterized by immunopathology that affects T-cell phenotype and functions. Previous studies found impaired T-cell response to phytohemagglutinin (PHA) in patients with acute tuberculosis. However, the influence of disease severity, affected T-cell subsets, and underlying mechanisms remain elusive.
Methods
Here we i...
Immune-based diagnosis of Buruli ulcer disease (BUD) in children is difficult due to cross-reactivity between mycobacteria. We found that T-cell IFNγ/TNFαresponses against Mycobacterium (M.) ulcerans and M. tuberculosis (PPDMulc, PPDMtub) were different between children with BUD (n=27) and TB (n=20) but only ratios (PPDMtub/PPDMulc) discriminated t...
Cerebral malaria (CM) is a rare but fatal form of severe malaria sequelae. Host-derived biomarkers have the potential to assist in the early assessment, diagnosis, and prognosis of CM. However, previously reported host-derived CM biomarkers have limited clinical utility despite their ability to discriminate between CM and non-CM conditions, either...
Background
Mycobacterium (M.) tuberculosis -caused immunopathology is characterized by aberrant expression of plasma cytokines in human tuberculosis. Disease severity and long-term anti-mycobacterial treatment are potentially influenced by immunopathology and normalization of plasma cytokine levels during therapy may indicate treatment efficacy and...
Background
Doxycycline is used for treatment of Mansonella (M.) perstans infection. Immune modulatory effects of both, M. perstans and doxycycline, have been described but long-term implications on host immune response are not defined. Here we determined multiple immune parameters of M. perstans infected individuals prior to and after doxycycline t...
Bacterial components and cytokines induce IL‐7 receptor (IL‐7Rα) expression in monocytes. Aberrant low IL‐7Rα expression of monocytes has been identified as a feature of tuberculosis immunopathology. Here, we investigated the mechanisms underlying IL‐7Rα regulation of monocytes and tuberculosis serum effects on IL‐7Rα expression.
Serum samples from...
Altered monocyte differentiation and effector functions characterize immune pathogenesis of tuberculosis. IL-7 is an important factor for proliferation of T cells and impaired IL-7 sensitivity due to decreased IL-7 receptor α-chain (IL-7Rα) expression was found in patients with acute tuberculosis. Peripheral blood monocytes have moderate IL-7Rα exp...
IFNγ-release assays (IGRAs) used for diagnosis of Mycobacterium (M.) tuberculosis infection have limited sensitivity. Alternative cytokines and M. tuberculosis latency-associated antigens may improve immune-based tests.
Multiplex cytokine analyses was done in culture supernatants after 6-day in vitro restimulation with M. tuberculosis IGRA and late...
Background
Cancer is the leading cause of death with 7.6 million deaths worldwide annually. About 19% of bladder cancer cases are attributed to environmental and occupational factors. The knowledge of any disease is very vital in the control or prevention of such disease. This study examined the knowledge and perception of urinary bladder cancer am...
We demonstrated impaired monocyte IL-7 receptor expression as well as IL-7 sensitivity in human tuberculosis with potential effects on anti-mycobacterial effector functions.
Suppressor of Cytokine Signaling (SOCS)3 is a crucial feedback inhibitor of several cytokine pathways with potential regulatory functions during T‐cell receptor activation. A role of SOCS3 in Interleukin (IL)‐7‐dependent homeostatic mechanisms has been assumed but the underlying mechanisms remain unclear. We investigated the role of SOCS3 in IL‐7 r...
IFN-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....
IFN-γ release assays [e.g., QuantiFERON (QFT)] are widely used for diagnosis of Mycobacterium tuberculosis (Mtb) infection. T-cell responses against QFT antigens ESAT6 and CFP10 are highly Mtb specific but previous studies indicated suboptimal assay sensitivity. Especially for potentially infected healthy contacts (HCs) of tuberculosis patients, al...
Nucleolar organiser regions (NORs) are loops of DNA which are responsible for ribosomal RNA (rRNA) transcription in the nucleus of cells. NORs can be selectively stained by silver methods. The NORs agyrophilia is due to a group of nucleolar proteins, which have affinity for silver (Agyrophilic Nucleolar Organizer Regions, AgNOR proteins). The aim o...
Background:
Iodine deficiency is a major public health problem affecting people worldwide, particularly pregnant women. Iodine requirements increase substantially during pregnancy making pregnant women vulnerable to iodine deficiency and its disorders such as abortions, stillbirths and pregnancy goitre as well as congenital abnormalities, cretinis...
T-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. Cons...
Background: Autophagy is an important biological process that is involved in cellular homeostasis and survival. Derailment of some cellular autophagic processes affects normal cellular function, resulting in cancers and other disorders. Autophagy related proteins are Beclin-1, a human tumour suppressor, Bcl-2 and p62 have been characterised in most...
Introduction
Myriad roles of mucins in normal tissues have been well documented, including lubrication of the epithelial surfaces; protection from physical damage; facilitation in cell-cell signaling and suppression of inflammatory activity. Pathological expression of mucins has been noted in cancer development and progression. This study sought to...
T-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 d...
Changes in plasma sIL-7R and plasma IL-7 during chemotherapy.
Absolute (left panel) and relative (right panel) differences of a) plasma sIL-7R and b) plasma IL-7 level after (6 months) and prior treatment for tuberculosis. Concentration of sIL-7R in plasma from TB patients was determined by cytometric bead array, while plasma IL-7 level was determi...
Surface level of IL-7R on CD3+CD4+ and CD3+CD4- cells.
Heparinised blood from TB patients (n = 22) and contacts to TB patients (n = 24) was lysed (RBC Lysis Buffer, Roche) and leukocytes were stained for CD3 APC (clone UCHT1, BD Biosciences), CD4 AlexaFluor 488 (clone RPTA-4, Biolegend) and IL-7R (CD127) PE-Cy7 (clone A019D5, Biolegend). Cells were...
STAT5 phosphorylation of CD4+ cells after IL-7 stimulation.
(a) Gating strategy for STAT5 phosphorylation (pSTAT5) on CD4+ cells stimulated with (solid line) or without (shaded) 10 ng/ml IL-7 for 15 min. Proportions (%) of cells in the individual gates are indicated, and mean fluorescence intensity (MFI) is shown for the two stimulations. (b) Titra...
Gating strategy for IFNγ+CD40L+ cells.
Gating strategy for IFNγ+CD40L+ cells of CD4+ cells after overnight stimulation of whole blood with PPD. Proportions (%) of cells in the individual gates are indicated.
(PDF)
Correlation between mIL-7R expression on T cells and plasma IL-7 or sIL-7R concentrations.
(EPS)
Gender differences in plasma sIL-7R levels.
Plasma concentrations of sIL-7R from TB contacts (n = 149) and tuberculosis patients prior to (0 months, n = 52), during (2 months, n = 46) and after (6 months, n = 41) treatment was determined by cytometric bead array. Exact Mann-Whitney U test used for comparison of gender differences.
(PDF)
Gating strategy for IL-7Rlow, and IL-7R MFI of CD4+ and CD8+ cells.
Proportions (%) of cells within the individual gates are indicated.
(PDF)
Unlabelled:
The hepatitis C virus (HCV; genus Hepacivirus) is a highly relevant human pathogen. Unique hepaciviruses (HV) were discovered recently in animal hosts. The direct ancestor of HCV has not been found, but the genetically most closely related animal HVs exist in horses. To investigate whether other peridomestic animals also carry HVs, we...
Unlabelled:
Bats have been implicated as reservoirs of emerging viruses. Bat species forming large social groups and roosting in proximity to human communities are of particular interest. In this study, we sampled a colony of ca. 350,000 individuals of the straw-colored fruit bat Eidolon helvum in Kumasi, the second largest city of Ghana. A novel...