Distribution of CL-K1 serum levels (median values) among the study groups (SEP: diagnosed with <i>S</i>. <i>haematobium</i> egg in urine; SELP: Negative for <i>S</i>. <i>haematobium</i> egg in urine but positive for anti-schistosoma total IgG; SELN: Negative for <i>S</i>. <i>haematobium</i> egg and anti-schistosoma total IgG).

<p><i>P</i> = 0.007 illustrated in the figure is calculated by Kruskal-Wallis rank sum test. Study group comparison were calculated by Dunn’s multiple comparison post test (SEP vs. SELN, <i>P<</i>0.001; SEP vs. SELP+SELN, <i>P</i>>0.05). Numbers in parentheses indicates absolute counts of sample size in each group.</p

Distribution of <i>COLEC11</i> haplotypes in the investigated study groups

<p>Note. CI, confidence interval; OR, odds ratio.</p><p>Percentage may not add up to 100 due to rounding errors</p><p>^# Adjusted <i>P</i> values for age and gender</p><p>^a diagnosed with <i>S</i>. <i>haematobium</i> egg in urine [SEP]</p><p>^b Negative for <i>S</i>. <i>haematobium</i> egg in urine but positive for anti-schistosoma total IgG [SELP]</p><p>^c Negative for <i>S</i>. <i>haematobium</i> egg and anti-schistosoma total IgG [SELN]</p><p>Distribution of <i>COLEC11</i> haplotypes in the investigated study groups</p

Linkage disequilibrium (LD) pattern of <i>COLEC11</i> variants in SEP cases group (A), in SELP control group (B), in SELN control group (C) and in SELP+SELN combined control group (D).

<p>Open white squares indicate a high degree of LD (D’ = 1) between pairs of markers. Numbers indicate the D’ value expressed as a percentile. The red square indicates pairs in strong LD with LOD scores ≥ 2; purple squares, D’ = 1 with LOD scores ≤ 1. The haplotype block is outlined by a solid line.</p

Distribution of <i>COLEC11—</i>rs7567833G/A (<i>p</i>.<i>R216H</i>) genotypes and allele(s).

<p><b>Note</b>. CI, confidence interval; OR, odds ratio.</p><p>Percentage may not add up to 100 due to rounding errors</p><p>^# Adjusted <i>P</i> values for age and gender</p><p>^a diagnosed with <i>S</i>. <i>haematobium</i> egg in urine [SEP]</p><p>^b Negative for <i>S</i>. <i>haematobium</i> egg in urine but positive for anti-schistosoma total IgG [SELP]</p><p>^c Negative for <i>S</i>. <i>haematobium</i> egg and anti-schistosoma total IgG [SELN]</p><p>Distribution of <i>COLEC11—</i>rs7567833G/A (<i>p</i>.<i>R216H</i>) genotypes and allele(s).</p

Distribution of CL-K1 serum levels (median values) with investigated rs7567833G/A (<i>p</i>.<i>R216H</i>) variant.

<p>(Left) SELN group (Right): SELP+SELN group. <i>P</i> = 0.03 and <i>P</i> = 0.001 illustrated in the figures are calculated by Kruskal-Wallis rank sum test. Study group comparison were calculated by Dunn’s multiple comparison post test (SELN-GG vs. SELN-AA, <i>P<</i>0.05; SELN-GA vs. SELN-AA, <i>P</i>>0.05); (SELN+SELP-GG vs. SELN+SELP-AA, <i>P</i><0.01; SELN+SELP-GA vs. SELN+SELP-AA, <i>P</i><0.05). Numbers in parentheses indicates absolute counts of sample size in each group. (<b>SEP</b>: diagnosed with <i>S</i>. <i>haematobium</i> egg in urine; <b>SELP</b>: Negative for <i>S</i>. <i>haematobium</i> egg in urine but positive for anti-schistosoma total IgG; <b>SELN</b>: Negative for <i>S</i>. <i>haematobium</i> egg and anti-schistosoma total IgG).</p

Distribution of CL-K1 serum levels (median values) with investigated <i>COLEC11*TCCA</i> haplotype in all study groups.

<p><i>P</i><0.0001 illustrated in the figure is calculated by Kruskal-Wallis rank sum test. Study group comparison were calculated by Dunn’s multiple comparison post test (<i>COLEC11*TCCA</i>-SEP vs. <i>COLEC11*TCCA</i>-SELN, <i>P</i><0.001; <i>COLEC11*TCCA</i>-SEP vs. <i>COLEC11*TCCA</i>-SELP+SELN, <i>P</i><0.01). Numbers in parentheses indicates absolute counts of sample size in each group. <b>SEP</b>: diagnosed with <i>S</i>. <i>haematobium</i> egg in urine; <b>SELP</b>: Negative for <i>S</i>. <i>haematobium</i> egg in urine but positive for anti-schistosoma total IgG; <b>SELN</b>: Negative for <i>S</i>. <i>haematobium</i> egg and anti-schistosoma total IgG.</p

Distribution of CL-K1 serum levels (median values) with investigated <i>COLEC11</i> haplotypes (Left) SELN controls (Right): SELP+SELN combined controls.

<p><i>P</i> = 0.03 and <i>P</i> = 0.0004 illustrated in the figures are calculated by Kruskal-Wallis rank sum test. Study group comparison were calculated by Dunn’s multiple comparison post test (<i>COLEC11*TCCG</i>-SELN vs. <i>COLEC11*TCCA</i>-SELN, <i>P<</i>0.05; <i>COLEC11*CCCG</i>-SELN vs. <i>COLEC11*TCCA</i>-SELN, <i>P>0</i>.<i>05</i>; <i>COLEC11*TCCG</i>-SELN+SELP vs. <i>COLEC11*TCCA</i>-SELN+SELP, <i>P<</i>0.001; <i>COLEC11*TCCG</i>-SELN+SELP vs. <i>COLEC11*CCCG</i>-SELN+SELP, <i>P></i>0.05). Numbers in parentheses indicate absolute counts of sample size in each group. <b>SEP</b>: diagnosed with <i>S</i>. <i>haematobium</i> egg in urine; <b>SELP</b>: Negative for <i>S</i>. <i>haematobium</i> egg in urine but positive for anti-schistosoma total IgG; <b>SELN</b>: Negative for <i>S</i>. <i>haematobium</i> egg and anti-schistosoma total IgG).</p

Reduced frequencies of mDC and pDC in blood from <i>S. haematobium</i>-infected subjects.

<p>(A) Blood DC were identified in fixed PBMC as HLA-DR⁺/CD14⁻/CD19⁻ cells and subsequently subdivided into mDC and pDC on the basis of positive staining for BDCA-1 and BDCA-2, respectively. Data from one representative donor is shown. (B) Frequencies of blood DC subsets in total PBMC (C) and their surface expression of HLADR, CD80, CD86 and CCR7 was determined by following the gating strategy shown in (A). (B) Box and whiskers with 10–90% percentile are shown. (C) Bars represent mean + SD. (B+C) Each group represents data from 20 donors.</p

mDC from <i>S. haematobium</i>-infected subjects have an altered MAPK signaling, but not TLR4 expression profile.

<p>(A) TLR4 expression was analysed on mDC present in PBMC following the gating strategy as described in legend of <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000667#pntd-0000667-g001" target="_blank">Fig. 1</a>. (B and C) 20 and 60 minutes after stimulation with LPS, mDC were intracellularly stained for (B) phospophorylated p38 and ERK and (C) the ratio between <i>p</i>-ERK and <i>p</i>-p38 was determined by dividing the respective mean fluorescence intensities per sample. Each group represents data from 5 donors. (A) Bars represent mean + SD. (B and C) box plots represent 25–75 percentile range with error bars showing minimum to maximum.</p

mDC from <i>S. haematobium</i>-infected subjects have a reduced T cell activating capacity due to lower HLA-DR expression.

<p>LPS matured mDC were cocultured with allogeneic naïve T helper cells for 6 d after which (A) T cell expansion was determined with a counting chamber and (B) Intracellular cytokine production or (C) CD25 and HLA-DR expression was assayed by FACS, 6 h after restimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin in the presence of brefeldin A for the last 2 h. (D+E) LPS-matured mDC from European controls were cocultured with allogeneic naïve T helper cells for 6 d in the presence of depicted neutralizing antibodies and T cells were counted as in (A). T cell counts are shown as (D) absolute values or (E) relative to the control condition. (A,B,D) Horizontal bars represent mean based on data from 9 donors in each group. (C) Box plots represent 25–75 percentile range with error bars showing minimum to maximum based data of 9 donors in each group. (E) Bars represent mean + SD of 3 independent experiments.</p