Innate immune cells and T CD4 cells profile during hepatitis B among HIV co-infection Beninese

Background: Worldwide, human immunodeficiency virus (HIV) infection remains a real public health. Hepatitis B virus (HBV) and HIV have the same routes of transmission and shared risk factors and epidemiology similarities. The purpose of this study was to assess the impact of HBV and HIV co-infection on T CD4 cells and innate immune cells.Methods: A cross-sectional and descriptive study was carried among 260 persons living with HIV (PLHIV) admitted and supported with antiviral tri therapy at the national reference center for research and Care of HIV infected person (NRCRC) of the national hospital and university center in Cotonou, Benin. After PLHIV peripheral blood collection, surface hepatitis B antigens (HBsAg) and HIV serology were tested using ELISA (Enzyme linked immuno sorbent assay). White blood cell count and leukocyte formula were performed using flow cytometry. After staining with anti CD4 antibodies, TCD4+ lymphocytes frequency was determined using flow cytometry. Means were calculated using student T test.Results: Of the 260 PLHIV, 10.77% (n=28) were co-infected with HBV. Our data has shown a significant decrease of lymphocytes among HIV and HBV co-infected persons and a very significant increase in immune innate cells including eosinophils, polynuclear basophils and monocytes, suggesting an important role of innate immune cells during HIV and HBV coinfection.Conclusion: HIV and HBV coinfection results in hyperinflammatory response associated with viral clearance. How this hyperinflammatory response is mounted was still unclear. More data are needed for better management of HIV and HBV co-infection

The humoral response to Plasmodium falciparum VarO rosetting variant and its association with protection against malaria in Beninese children

<p>Abstract</p> <p>Background</p> <p>The capacity of <it>Plasmodium falciparum</it>-infected erythrocytes to bind uninfected erythrocytes (rosetting) is associated with severe malaria in African children. Rosetting is mediated by a subset of the variant surface antigens PfEMP1 targeted by protective antibody responses. Analysis of the response to rosette-forming parasites and their PfEMP1 adhesive domains is essential for understanding the acquisition of protection against severe malaria. To this end, the antibody response to a rosetting variant was analysed in children recruited with severe or uncomplicated malaria or asymptomatic <it>P. falciparum </it>infection.</p> <p>Methods</p> <p>Serum was collected from Beninese children with severe malaria, uncomplicated malaria or <it>P. falciparum </it>asymptomatic infection (N = 65, 37 and 52, respectively) and from immune adults (N = 30) living in the area. Infected erythrocyte surface-reactive IgG, rosette disrupting antibodies and IgG to the parasite crude extract were analysed using the single variant Palo Alto VarO-infected line. IgG, IgG1 and IgG3 to PfEMP1-varO-derived NTS-DBL1α₁, CIDRγ and DBL2βC2 recombinant domains were analysed by ELISA. Antibody responses were compared in the clinical groups. Stability of the response was studied using a blood sampling collected 14 months later from asymptomatic children.</p> <p>Results</p> <p>Seroprevalence of erythrocyte surface-reactive IgG was high in adults (100%) and asymptomatic children (92.3%) but low in children with severe or uncomplicated malaria (26.1% and 37.8%, respectively). The IgG, IgG1 and IgG3 antibody responses to the varO-derived PfEMP1 domains were significantly higher in asymptomatic children than in children with clinical malaria in a multivariate analysis correcting for age and parasite density at enrolment. They were essentially stable, although levels tended to decrease with time. VarO-surface reactivity correlated positively with IgG reactivity to the rosetting domain varO-NTS-DBL1α₁. None of the children sera, including those with surface-reactive antibodies possessed anti-VarO-rosetting activity, and few adults had rosette-disrupting antibodies.</p> <p>Conclusions</p> <p>Children with severe and uncomplicated malaria had similar responses. The higher prevalence and level of VarO-reactive antibodies in asymptomatic children compared to children with malaria is consistent with a protective role for anti-VarO antibodies against clinical falciparum malaria. The mechanism of such protection seems independent of rosette-disruption, suggesting that the cytophilic properties of antibodies come into play.</p

Association of IL-4 and IL-10 maternal haplotypes with immune responses to P. falciparum in mothers and newborns

Abstract Background: Particular cytokine gene polymorphisms are involved in the regulation of the antibody production. The consequences of already described IL-4, IL-10 and IL-13 gene polymorphisms on biological parameters and antibody levels were investigated among 576 mothers at delivery and their newborns in the context of P. falciparum placental malaria infection. Methods: The study took place in the semi-rural area of Tori-Bossito, in south-west Benin, where malaria is meso-endemic. Six biallelic polymorphisms were determined by quantitative PCR using TaqMan W Pre-Designed SNP Genotyping Assays, in IL-4 (rs2243250, rs2070874), IL-10 (rs1800896, rs1800871, rs1800872) and IL-13 (rs1800925) genes. Antibody responses directed to P. falciparum MSP-1, MSP-2, MSP-3, GLURP-R0, GLURP-R2 and AMA-1 recombinant proteins were determined by ELISA. Results: The maternal IL-4 −590 *T/IL-4 +33 *T haplotype (one or two copies) was associated with favorable maternal condition at delivery (high haemoglobin levels, absence of placental parasites) and one of its component, the IL-4 −590 TT genotype, was related to low IgG levels to MSP-1, MSP-2/3D7 and MSP-2/FC27. Inversely, the maternal IL-10 −1082 AA was positively associated with P. falciparum placenta infection at delivery. As a consequence, the IL-10 −819 *T allele (in CT and TT genotypes) as well as the IL-10 −1082 *A/IL-10 −819 *T/IL-10 −592 *A haplotype (one or two copies) in which it is included, were related to an increased risk for anaemia in newborns. The maternal IL-10 −1082 AA genotype was related to high IgG levels to MSP-2/3D7 and AMA-1 in mothers and newborns, respectively. The IL-13 gene polymorphism was only involved in the newborn&apos;s antibody response to AMA-1. Conclusion: These data revealed that IL-4 and IL-10 maternal gene polymorphisms are likely to play a role in the regulation of biological parameters in pregnant women at delivery (anaemia, P. falciparum placenta infection) and in newborns (anaemia). Moreover, IL-4, IL-10 and IL-13 maternal gene polymorphisms were related to IgG responses to MSP-1, MSP-2/3D7 and MSP-2/FC27 in mothers as well as to AMA-1 in newborns

Implication of Human Endogenous Retrovirus Envelope Proteins in Placental Functions

Human endogenous retroviruses (ERVs) represent 8% of the total human genome. Although the majority of these ancient proviral sequences have only retained non-coding long terminal repeats (LTRs), a number of “endogenized” retroviral genes encode functional proteins. Previous studies have underlined the implication of these ERV-derived proteins in the development and the function of the placenta. In this review, we summarize recent findings showing that two ERV genes, termed Syncytin-1 and Syncytin-2, which encode former envelope (Env) proteins, trigger fusion events between villous cytotrophoblasts and the peripheral multinucleated syncytiotrophoblast layer. Such fusion events maintain the stability of this latter cell structure, which plays an important role in fetal development by the active secretion of various soluble factors, gas exchange and regulation of fetomaternal immunotolerance. We also highlight new studies showing that these ERV proteins, in addition to their localization at the cell surface of cytotrophoblasts, are also incorporated on the surface of various extracellular microvesicles, including exosomes. Such exosome-associated proteins could be involved in the various functions attributed to these vesicles and could provide a form of tropism. Additionally, through their immunosuppressive domains, these ERV proteins could also contribute to fetomaternal immunotolerance in a local and more distal manner. These various aspects of the implication of Syncytin-1 and -2 in placental function are also addressed in the context of the placenta-related disorder, preeclampsia

Contrôle génétique de la réponse anticorps antipalustre dans le cas du paludisme placentaire et du paludisme de l'enfant, au Bénin

Ce travail présente les réponses anticorps antipalustres de femmes enceintes, de nouveau-nés et de jeunes enfants du sud du Bénin en fonction de certains polymorphismes des gènes codant pour les interleukines IL-4, IL-10, IL-13 et en fonction des allotypes Gm et Km des immunoglobulines. Des données originales sont présentées dans cette thèse pour une cohorte de mères, de leurs nouveau-nés et d autres enfants du sud du Bénin. Notre étude s appuie sur des données cliniques, parasitologiques et biologiques obtenues pour tous ces individus. La distribution des génotypes de cytokines montre une proximité génétique entre les femmes de Tori Bossito au Bénin et la population Yoruba du Nigéria. Les polymorphismes maternels IL-4-590*C/T et IL-4+33*C/T sont associés à des niveaux variables de densités parasitaires placentaires et d hémoglobine chez les mères à l accouchement. Ces polymorphismes et ceux localisés en -1082 et -592 du gène de l IL-10 de la mère sont associés à des niveaux variables d IgG et IgM spécifiques d antigènes palustres chez les mères et leurs fœtus. L exploration de la réponse anticorps anti-VarO chez des enfants symptomatiques et asymptomatiques du sud du Bénin, a montré l existence d une production accrue d anticorps contre différents domaines du variant VarO de la protéine PfEMP1 chez les enfants asymptomatiques. Enfin, l analyse du rôle des allotypes Gm et Km des immunoglobulines dans la réponse immunologique au paludisme chez ces enfants révèle l amplification d une immunité naturelle anti-VarO jusqu à l âge de 4 ans pour ceux qui portent le phénotype Gm 5,6,13,14 ; 1,17 précédemment associé à la protection clinique contre le paludisme chez ces enfants.This work described anti-malaria antibody responses in Beninese pregnant women and their newborns as well as young children according to IL-4, IL-10 and IL-13 gene polymorphisms or Gm and Km immunoglobulin allotypes. Our study is based on clinical, parasitological and biological data obtained for all individuals. Cytokine genotypes distribution was similar among women from Tori-Bossito in Benin as in a reference population of Yoruba from Nigeria. Maternal polymorphisms IL-4-590*C/T and IL-4+33*C/T were associated with variable placental parasite densities and haemoglobin levels in mothers at delivery. These polymorphisms and those located at -1082 and -592 in maternal IL-10 gene were associated with variable anti-malaria IgG and IgM levels in mothers and their newborns. Exploration of PfEMP1/VarO antibody response in symptomatic and asymptomatic children from southern Benin showed higher antibody levels directed to different PfEMP1/VarO domains in asymptomatic children. Finally, analysis of the role of Gm and Km immunoglobulin allotypes in the immune response to malaria among these children revealed an amplification of the anti-VarO antibody response until the age of 4 years for children carrying the Gm 5,6,13,14; 1,17 phenotype that was already related to clinical protection against malaria in the same children.PARIS-BIUP (751062107) / SudocSudocFranceF

Association of IL-4 and IL-10 maternal haplotypes with immune responses to P. falciparum in mothers and newborns

PRIFPRI3; ISI; B Promoting healthy food systems; G Cross-cutting gender themePHN

A CRE/AP-1-like motif is essential for induced syncytin-2 expression and fusion in human trophoblast-like model.

Syncytin-2 is encoded by the envelope gene of Endogenous Retrovirus-FRD (ERVFRD-1) and plays a critical role in fusion of placental trophoblasts leading to the formation of the multinucleated syncytiotrophoblast. Its expression is consequently regulated in a strict manner. In the present study, we have identified a forskolin-responsive region located between positions -300 to -150 in the Syncytin-2 promoter region. This 150 bp region in the context of a minimal promoter mediated an 80-fold induction of promoter activity following forskolin stimulation. EMSA analyses with competition experiments with nuclear extracts from forskolin-stimulated BeWo cells demonstrated that the -211 to -177 region specifically bound two forskolin-induced complexes, one of them containing a CRE/AP-1-like motif. Site-directed mutagenesis of the CRE/AP-1 binding site in the context of the Syncytin-2 promoter or a heterologous promoter showed that this motif was mostly essential for forskolin-induced promoter activity. Transfection experiments with dominant negative mutants and constitutively activated CREB expression vectors in addition to Chromatin Immunoprecipitation suggested that a CREB family member, CREB2 was binding and acting through the CRE/AP-1 motif. We further demonstrated the binding of JunD to this same motif. Similar to forskolin and soluble cAMP, CREB2 and JunD overexpression induced Syncytin-2 promoter activity in a CRE/AP-1-dependent manner and Syncytin-2 expression. In addition, BeWo cell fusion was induced by both CREB2 and JunD overexpression, while being repressed following silencing of either gene. These results thereby demonstrate that induced expression of Syncytin-2 is highly dependent on the interaction of bZIP-containing transcription factors to a CRE/AP-1 motif and that this element is important for the regulation of Syncytin-2 expression, which results in the formation of the peripheral syncytiotrophoblast layer

Identification of a CRE/AP-1-like motif and GATA-binding site within the Syncytin-2 promoter.

<p><b>(A)</b> Extended probe 5 (termed WT) (from-211 to-177) (indicated in the upper part of the panel) was used for EMSA analyses and highlights the CRE/AP-1-like motif and the potential GATA-binding site in the Syncytin-2 promoter. Nuclear extracts from BeWo cells treated (T) or not (NT) with forskolin for 15 min were pre-incubated with different concentrations of cold specific or non-specific oligonucleotides prior to addition of the labeled WT probe. (<b>B</b>) EMSA analyses of nuclear extracts from BeWo cells stimulated with forskolin at different time points and incubated with the WT probe. <b>(C)</b> Representation of the various oligonucleotides bearing mutated sequences (nucleotides in italic) used in EMSA analyses. <b>(D-E)</b> Nuclear extracts from non-treated (NT) or forskolin-treated (T) BeWo cells were incubated with the WT probe and excess (100X) cold WT or mutated oligonucleotides presented in (<b>C</b>). Specific DNA-protein complexes are indicated on left side of panels. (<b>F</b>) Nuclear extracts from primary villous cytotrophoblasts cultured for 24 and 96 hours were incubated with the WT probe and with or without excess (100X) cold WT oligonucleotide.</p