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Sökning: WFRF:(Ndam Nicaise Tuikue)

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1.
  • Gbedande, Komi, et al. (författare)
  • Infections with Plasmodium falciparum during pregnancy affect VAR2CSA DBL-5 domain-specific T cell cytokine responses
  • 2016
  • Ingår i: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Current knowledge of human immunological responses to pregnancy-associated malaria-specific Plasmodium falciparum protein VAR2CSA concerns almost exclusively B cell-driven antibody-mediated activity. Knowledge of VAR2CSA-specific T cell-mediated activity is minimal by comparison, with only a single published report of a study investigating VAR2CSA-derived peptide-specific T cell responses. The study described here represents an attempt to redress this balance. Methods: Within the framework of a cohort study of 1037 pregnant Beninese, sub-groups were selected on the basis of the documented presence/absence of infection with P. falciparum and conducted detailed immunological assessments both at inclusion into the study and at delivery. Peripheral blood mononuclear cells were isolated, stimulated in vitro, and VAR2CSA DBL-5 domain-specific, IFN-gamma-secreting T-cell frequencies and cytokine responses were quantified using flow cytometric techniques. Multivariate analyses were used to determine primarily whether the T cell-mediated DBL5-specific activity measured was associated with infection by P. falciparum adjusted for gravidity, anaemia and other cofactors. Results: Infections with P. falciparum detected at inclusion were associated with enhanced non-specific TNF responses, whilst diminished non-specific and DBL-5-specific IL-10 responses were associated with infections detected at delivery. Infections during pregnancy led to enhanced non-specific and DBL-5-specific IFN-gamma responses detectable at delivery but to concomitantly lower DBL-5-specific CD8+ IFN-gamma responses. Prospective assessments indicated that non-specific pro-inflammatory responses detectable at inclusion in the study were associated with the occurrence of infections subsequently during pregnancy. Conclusions: The findings represent a first step in elucidating the quantity and quality of cellular immunological responses to VAR2CSA, which will help in the development of the primary vaccine candidate for prevention of pregnancy-associated malaria.
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2.
  • Ibitokou, Samad A., et al. (författare)
  • Submicroscopic Infections with Plasmodium falciparum during Pregnancy and Their Association with Circulating Cytokine, Chemokine, and Cellular Profiles
  • 2014
  • Ingår i: Clinical and Vaccine Immunology. - 1556-6811 .- 1556-679X. ; 21:6, s. 859-866
  • Tidskriftsartikel (refereegranskat)abstract
    • The immunological consequences of pregnancy-associated malaria (PAM) due to Plasmodium falciparum have been extensively investigated in cross-sectional studies conducted at delivery, but there have been very few longitudinal studies of changes due to PAM during pregnancy. We conducted a prospective study in Benin to investigate the changes associated with PAM in groups of 131 and 111 women at inclusion in the second trimester and at delivery, respectively. Infected women were identified by standard microscopic examinations of blood smears and by quantitative PCR (qPCR) assays and were matched to uninfected control women by age, gestational age, and gravidity. We quantified plasma levels of a panel of soluble immunological mediators and other mediators, as well as the frequencies of peripheral blood mononuclear cell types. Comparisons of these variables in infected and uninfected women used multivariate analyses, and we also assessed the predictive value of variables measured at inclusion for pregnancy outcomes at delivery. In multivariate analyses, peripheral plasma interleukin 10 (IL-10) and gamma interferon-inducible protein 10 (IP-10) levels were associated with PAM at inclusion and at delivery, while higher IL-10 levels distinguished qPCR-detectable submicroscopic infections at inclusion but not at delivery. Maternal anemia at delivery was associated with markers of proinflammatory (increased frequency of monocytes) and anti-inflammatory (increased IL-10 levels and increased activation of regulatory T cells) activity measured at inclusion. Elevated concentrations of IL-10 are associated with the majority of P. falciparum infections during pregnancy, but this marker alone does not identify all submicroscopic infections. Reliably identifying such occult infections will require more sensitive and specific methods.
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