Multivariable logistic regression analysis for delivery of an infant with low birth weight.

<p>LBW = low birth weight, OR = Odds Ratio, IPTp = intermittent preventive treatment of malaria during pregnancy.</p

Univariable analysis of adolescent compared to adult women.

<p>LBW = low birth weight, IPTp = intermittent preventive treatment of malaria during pregnancy.</p

Birth weight of term-newborns born to adolescent and adult mothers for each week of gestation.

<p>Bars show mean birth weight and standard deviations for adolescent (≤16 years) and adult (>16 years) mothers.</p

CD4⁺CD25^hiFOXP3⁺ Regulatory T Cells and Cytokine Responses in Human Schistosomiasis before and after Treatment with Praziquantel

<div><p>Background</p><p>Chronic schistosomiasis is associated with T cell hypo-responsiveness and immunoregulatory mechanisms, including induction of regulatory T cells (Tregs). However, little is known about Treg functional capacity during human <i>Schistosoma haematobium</i> infection.</p><p>Methodology</p><p>CD4⁺CD25^hiFOXP3⁺ cells were characterized by flow cytometry and their function assessed by analysing total and Treg-depleted PBMC responses to schistosomal adult worm antigen (AWA), soluable egg antigen (SEA) and Bacillus Calmette-Guérin (BCG) in <i>S</i>. <i>haematobium</i>-infected Gabonese children before and 6 weeks after anthelmintic treatment. Cytokines responses (IFN-γ, IL-5, IL-10, IL-13, IL-17 and TNF) were integrated using Principal Component Analysis (PCA). Proliferation was measured by CFSE.</p><p>Principal Findings</p><p><i>S</i>. <i>haematobium</i> infection was associated with increased Treg frequencies, which decreased post-treatment. Cytokine responses clustered into two principal components reflecting regulatory and Th2-polarized (PC1) and pro-inflammatory and Th1-polarized (PC2) cytokine responses; both components increased post-treatment. Treg depletion resulted in increased PC1 and PC2 at both time-points. Proliferation on the other hand, showed no significant difference from pre- to post-treatment. Treg depletion resulted mostly in increased proliferative responses at the pre-treatment time-point only.</p><p>Conclusions</p><p><i>Schistosoma</i>-associated CD4⁺CD25^hiFOXP3⁺Tregs exert a suppressive effect on both proliferation and cytokine production. Although Treg frequency decreases after praziquantel treatment, their suppressive capacity remains unaltered when considering cytokine production whereas their influence on proliferation weakens with treatment.</p></div

Principal component analysis (PCA) of cytokine responses to schistosome specific and non-specific antigens.

<p>Two distinct principal components were identified: principal component 1 (PC1) which reflects regulatory and Th2-polarized cytokine responses due to its positive loading with IL-5, IL-10 and IL-13 responses; and principal component 2 (PC2) which reflects pro-inflammatory and Th1-polarized cytokine responses due to its positive loading with IFN-γ, IL-17 and TNF.</p

Description of principal components.

<p>Arbitrary values indicate the relative loading of each cytokine response towards each principal component. Strong positive loadings (>0.500) are indicated in bold. IL, interleukin; IFN, interferon; TNF, tumor necrosis factor.</p><p>Description of principal components.</p

Proliferative responses to schistosome specific and non-specific antigens.

<p>CFSE-labelled total PBMC from <i>S</i>. <i>haematobium</i> infected children pre- and 6 weeks post-treatment were left unstimulated (medium), or stimulated with <i>S</i>. <i>haematobium</i> adult worm antigen (AWA) and soluble egg antigen (SEA) and Bacillus Calmette–Guérin (BCG). After 4 days of culture cells were fixed, cryopreserved and after thawing CFSE division was analyzed for CD4⁺CD25^hi T cells by flow cytometry. Results are shown as median with IQR. Differences between pre-treatment and 6 weeks post-treatment responses were tested with a Wilcoxon matched pairs test.</p

Increased frequency of CD4⁺CD25^hiFOXP3⁺ Tregs during S. haematobium infection.

<p>Gating strategy for identification of CD4⁺CD25^hiFOXP3⁺ Tregs (A). CD4 T cells were identified and Boolean gating combinations were used to determine proportions of CD4⁺CD25^hiFOXP3⁺ Tregs (B). Differences between groups were tested with a Mann-Whitney U test and within groups with a Wilcoxon matched pairs test. Horizontal bars represent median. * p< 0.05, ** p< 0.01.</p

CD4⁺CD25^hiFOXP3⁺ Cells in Cord Blood of Neonates Born from Filaria Infected Mother Are Negatively Associated with CD4⁺Tbet⁺ and CD4⁺RORγt⁺ T Cells

<div><p>Background</p><p>Children who have been exposed <i>in utero</i> to maternal filarial infection are immunologically less responsive to filarial antigens, have less pathology, and are more susceptible to acquire infection than offspring of uninfected mothers. Moreover children from filaria infected mothers have been shown to be less responsive to vaccination as a consequence of an impairment of their immune response. However, it is not well known how <i>in utero</i> exposure to parasite antigens affects cellular immune responses.</p><p>Methodology</p><p>Here, 30 pregnant women were examined for the presence of microfilaria of <i>Loa loa</i> and <i>Mansonella perstans</i> in peripheral blood. At delivery, cord blood mononuclear cells (CBMC) were obtained and the CD4⁺T cells were phenotyped by expression of the transcription factors Tbet, RORγt, and FOXP3.</p><p>Results</p><p>No significant difference was observed between newborns from infected versus uninfected mothers in the frequencies of total CD4⁺T cells and CD4⁺T cells subsets including CD4⁺Tbet⁺, CD4⁺RORγt⁺ T and CD4⁺CD25^hiFOXP3⁺ T cells. However, there was a negative association between CD4⁺CD25^hiFOXP3⁺T cells and CD4⁺Tbet⁺ as well as CD4⁺RORγt⁺ T cells in the infected group only (B = −0.242, P = 0.002; B = −0.178, P = 0.013 respectively).</p><p>Conclusion</p><p>Our results suggest that filarial infection during pregnancy leads to an expansion of functionally active regulatory T cells that keep TH1 and TH17 in check.</p></div

Baseline characteristic of the mother and the children enrolled in the study.

#<p>Mann-Withney test.</p>##<p>Fisher exact test.</p>###<p>Independent sample t-test.</p><p>Baseline characteristic of the mother and the children enrolled in the study.</p