Antioxidant potentiality of three herbal teas consumed in Bandundu rural areas of Congo.

peer reviewedThe aim of this study was to evaluate and compare the cellular antioxidant activities of Lantana montevidensis, Lippia multiflora, and Ocimum gratissimum leaves often consumed as herbal teas in a rural area of Bandundu severely affected by konzo, which is related to oxidative damage. Consequently, dietary supplements with proven antioxidant potentialities could be of real interest to promote in this area. Phytochemical screening by TLC and HPLC-DAD of extracts revealed the presence of verbascoside as a major phenolic compound. Verbascoside in L. montevidensis and O. gratissimum is reported here for the first time. All extracts displayed high ABTS and DPPH radical-scavenging activities at the concentration range of 1-40 mug mL-1 according to order: L. multiflora > O. gratissimum > L. montevidensis. L. multiflora showed the best cellular antioxidant activity using DCFH-DA on HL-60 monocytes assay at 1-20 mug mL-1. These herbal teas may be used as nutraceuticals for their potent antioxidant activity

γδ T cells control murine skin inflammation and subcutaneous adipose wasting during chronic Trypanosoma brucei infection

African trypanosomes colonise the skin to ensure parasite transmission. However, how the skin responds to trypanosome infection remains unresolved. Here, we investigate the local immune response of the skin in a murine model of infection using spatial and single cell transcriptomics. We detect expansion of dermal IL-17A-producing Vγ6+ cells during infection, which occurs in the subcutaneous adipose tissue. In silico cell-cell communication analysis suggests that subcutaneous interstitial preadipocytes trigger T cell activation via Cd40 and Tnfsf18 signalling, amongst others. In vivo, we observe that female mice deficient for IL-17A-producing Vγ6+ cells show extensive inflammation and limit subcutaneous adipose tissue wasting, independently of parasite burden. Based on these observations, we propose that subcutaneous adipocytes and Vγ6+ cells act in concert to limit skin inflammation and adipose tissue wasting. These studies provide new insights into the role of γδ T cell and subcutaneous adipocytes as homeostatic regulators of skin immunity during chronic infection

High-depth African genomes inform human migration and health

The African continent is regarded as the cradle of modern humans and African genomes contain more genetic variation than those from any other continent, yet only a fraction of the genetic diversity among African individuals has been surveyed1. Here we performed whole-genome sequencing analyses of 426 individuals—comprising 50 ethnolinguistic groups, including previously unsampled populations—to explore the breadth of genomic diversity across Africa. We uncovered more than 3 million previously undescribed variants, most of which were found among individuals from newly sampled ethnolinguistic groups, as well as 62 previously unreported loci that are under strong selection, which were predominantly found in genes that are involved in viral immunity, DNA repair and metabolism. We observed complex patterns of ancestral admixture and putative-damaging and novel variation, both within and between populations, alongside evidence that Zambia was a likely intermediate site along the routes of expansion of Bantu-speaking populations. Pathogenic variants in genes that are currently characterized as medically relevant were uncommon—but in other genes, variants denoted as ‘likely pathogenic’ in the ClinVar database were commonly observed. Collectively, these findings refine our current understanding of continental migration, identify gene flow and the response to human disease as strong drivers of genome-level population variation, and underscore the scientific imperative for a broader characterization of the genomic diversity of African individuals to understand human ancestry and improve health

High-depth African genomes inform human migration and health

The African continent is regarded as the cradle of modern humans and African genomes contain more genetic variation than those from any other continent, yet only a fraction of the genetic diversity among African individuals has been surveyed1. Here we performed whole-genome sequencing analyses of 426 individuals—comprising 50 ethnolinguistic groups, including previously unsampled populations—to explore the breadth of genomic diversity across Africa. We uncovered more than 3 million previously undescribed variants, most of which were found among individuals from newly sampled ethnolinguistic groups, as well as 62 previously unreported loci that are under strong selection, which were predominantly found in genes that are involved in viral immunity, DNA repair and metabolism. We observed complex patterns of ancestral admixture and putative-damaging and novel variation, both within and between populations, alongside evidence that Zambia was a likely intermediate site along the routes of expansion of Bantu-speaking populations. Pathogenic variants in genes that are currently characterized as medically relevant were uncommon—but in other genes, variants denoted as ‘likely pathogenic’ in the ClinVar database were commonly observed. Collectively, these findings refine our current understanding of continental migration, identify gene flow and the response to human disease as strong drivers of genome-level population variation, and underscore the scientific imperative for a broader characterization of the genomic diversity of African individuals to understand human ancestry and improve health

DNA methylation patterns associated with konzo in Sub-Saharan Africa

Konzo, a disease characterized by sudden, irreversible spastic paraparesis, affecting up to 10% of the population in some regions of Sub-Saharan Africa during outbreaks, is strongly associated with dietary exposure to cyanogenic bitter cassava. The molecular mechanisms underlying the development of konzo remain largely unknown. Here, through an analysis of 16 individuals with konzo and matched healthy controls from the same outbreak zones, we identified 117 differentially methylated loci involved in numerous biological processes that may identify cyanogenic-sensitive regions of the genome, providing the first study of epigenomic alterations associated with a clinical phenotype of konzo

Molecular identification of Plasmodium species in symptomatic children of Democratic Republic of Congo

Abstract Background Worldwide, the highest malaria mortality is due to Plasmodium falciparum infection. However, other species of Plasmodium (Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, and Plasmodium knowlesi) can also cause malaria. Therefore, accurate identification of malaria species is crucial for patient management and epidemiological surveillance. This study aimed to determine the different Plasmodium species causing malaria in children under 5 years old in two provinces (Kinshasa and North Kivu) of the Democratic Republic of Congo (DRC). Methods From October to December 2015, a health-facility based cross-sectional study was conducted in General Reference Hospitals in Kinshasa and North Kivu. Four hundred and seven blood samples were collected from febrile children aged ≤ 5 years. Nested polymerase chain reaction assays were performed for Plasmodium species identification. Results Out of 407 children, 142 (34.9%) were infected with Plasmodium spp. and P. falciparum was the most prevalent species (99.2%). Among those infected children, 124 had a mono infection with P. falciparum and one with P. malariae. Mixed infections with P. falciparum/P. malariae and P. falciparum/P. vivax were observed in 6 (1.5%) and 8 (2.0%) children, respectively. The prevalence of infection was higher in females (64.8%) than in males (35.2%), p < 0.001. The age-specific distribution of infection showed that children of less than 2 years old were less infected (18.4%) compared to those aged above 2 years (81.6%), p < 0.001. Conclusion Although this study showed clearly that the most prevalent species identified was P. falciparum, the findings demonstrate the existence of non-falciparum malaria, especially P. malariae and P. vivax among children aged ≤ 5 years living both Kinshasa and North Kivu Provinces in DRC

The murine meninges acquire lymphoid tissue properties and harbour autoreactive B cells during chronic Trypanosoma brucei infection

The meningeal space is a critical brain structure providing immunosurveillance for the central nervous system (CNS), but the impact of infections on the meningeal immune landscape is far from being fully understood. The extracellular protozoan parasite Trypanosoma brucei, which causes human African trypanosomiasis (HAT) or sleeping sickness, accumulates in the meningeal spaces, ultimately inducing severe meningitis and resulting in death if left untreated. Thus, sleeping sickness represents an attractive model to study immunological dynamics in the meninges during infection. Here, by combining single-cell transcriptomics and mass cytometry by time-of-flight (CyTOF) with in vivo interventions, we found that chronic T. brucei infection triggers the development of ectopic lymphoid aggregates (ELAs) in the murine meninges. These infection-induced ELAs were defined by the presence of ER-TR7+ fibroblastic reticular cells, CD21/35+ follicular dendritic cells (FDCs), CXCR5+ PD1+ T follicular helper-like phenotype, GL7+ CD95+ GC-like B cells, and plasmablasts/plasma cells. Furthermore, the B cells found in the infected meninges produced high-affinity autoantibodies able to recognise mouse brain antigens, in a process dependent on LTβ signalling. A mid-throughput screening identified several host factors recognised by these autoantibodies, including myelin basic protein (MBP), coinciding with cortical demyelination and brain pathology. In humans, we identified the presence of autoreactive IgG antibodies in the cerebrospinal fluid (CSF) of second stage HAT patients that recognised human brain lysates and MBP, consistent with our findings in experimental infections. Lastly, we found that the pathological B cell responses we observed in the meninges required the presence of T. brucei in the CNS, as suramin treatment before the onset of the CNS stage prevented the accumulation of GL7+ CD95+ GC-like B cells and brain-specific autoantibody deposition. Taken together, our data provide evidence that the meningeal immune response during chronic T. brucei infection results in the acquisition of lymphoid tissue-like properties, broadening our understanding of meningeal immunity in the context of chronic infections. These findings have wider implications for understanding the mechanisms underlying the formation ELAs during chronic inflammation resulting in autoimmunity in mice and humans, as observed in other autoimmune neurodegenerative disorders, including neuropsychiatric lupus and multiple sclerosis

The murine meninges acquire lymphoid tissue properties and harbour autoreactive B cells during chronic Trypanosoma brucei infection

The meningeal space is a critical brain structure providing immunosurveillance for the central nervous system (CNS), but the impact of infections on the meningeal immune landscape is far from being fully understood. The extracellular protozoan parasite Trypanosoma brucei, which causes human African trypanosomiasis (HAT) or sleeping sickness, accumulates in the meningeal spaces, ultimately inducing severe meningitis and resulting in death if left untreated. Thus, sleeping sickness represents an attractive model to study immunological dynamics in the meninges during infection. Here, by combining single-cell transcriptomics and mass cytometry by time-of-flight (CyTOF) with in vivo interventions, we found that chronic T. brucei infection triggers the development of ectopic lymphoid aggregates (ELAs) in the murine meninges. These infection-induced ELAs were defined by the presence of ER-TR7+ fibroblastic reticular cells, CD21/35+ follicular dendritic cells (FDCs), CXCR5+ PD1+ T follicular helper-like phenotype, GL7+ CD95+ GC-like B cells, and plasmablasts/plasma cells. Furthermore, the B cells found in the infected meninges produced high-affinity autoantibodies able to recognise mouse brain antigens, in a process dependent on LTβ signalling. A mid-throughput screening identified several host factors recognised by these autoantibodies, including myelin basic protein (MBP), coinciding with cortical demyelination and brain pathology. In humans, we identified the presence of autoreactive IgG antibodies in the cerebrospinal fluid (CSF) of second stage HAT patients that recognised human brain lysates and MBP, consistent with our findings in experimental infections. Lastly, we found that the pathological B cell responses we observed in the meninges required the presence of T. brucei in the CNS, as suramin treatment before the onset of the CNS stage prevented the accumulation of GL7+ CD95+ GC-like B cells and brain-specific autoantibody deposition. Taken together, our data provide evidence that the meningeal immune response during chronic T. brucei infection results in the acquisition of lymphoid tissue-like properties, broadening our understanding of meningeal immunity in the context of chronic infections. These findings have wider implications for understanding the mechanisms underlying the formation ELAs during chronic inflammation resulting in autoimmunity in mice and humans, as observed in other autoimmune neurodegenerative disorders, including neuropsychiatric lupus and multiple sclerosis

Introducing the TrypanoGEN biobank: A valuable resource for the elimination of human African trypanosomiasis

No abstract available