Lectin complement protein Collectin 11 (CL-K1) and susceptibility to urinary schistosomiasis

Abstract

Background: Urinary Schistosomiasis is a neglected tropical disease endemic in many sub Saharan -African countries. Collectin Kidney 1 (CL-K1, encoded by COLEC11 on chromosome 2p25.3), a member of the vertebrate C-type lectin super family, has recently been identified as pattern-recognition molecule (PRR) of the lectin complement pathway. CL-K1 is preferentially expressed in the kidneys, but also in other organs and it is considered to play a role in host defense to some infectious agents. Schistosome teguments are fucosylated and CL-K1 has, through its collagen-like domain, a high binding affinity to fucose.

Methodology/principal findings: We utilized a Nigerian study group consisting of 167 Schistosoma haematobium infected individuals and 186 matched healthy subjects, and investigated the contribution of CL-K1 deficiency and of COLEC11 polymorphisms to infection phenotype. Higher CL-K1 serum levels were associated with decreased risk of schistosome infection (P corr = 0.0004). CL-K1 serum levels were differentially distributed between the COLEC11 genotypes and haplotypes observed. The non-synonymous variant p.R216H was associated with the occurrence of schistosomiasis (OR = 0.44, 95%CI = 0.22-0.72, P corr = 0.0004). The reconstructed COLEC11*TCCA haplotypes were associated with higher CL-K1 serum levels (P = 0.002) and with decreased schistosomiasis (OR = 0.38, 95%CI = 0.23-0.63, P corr = 0.0001).

Conclusions: In agreement with findings from our earlier published study, our findings support the observation that CL-K1 and their functional variants may be host factors associated with protection in schistosomiasis and may be a useful marker for further investigations.

Fig 1. Linkage disequilibrium (LD) pattern of COLEC11 variants in SEP cases group (A), in SELP control group (B), in SELN control group (C) and in SELP+SELN combined control group (D).

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.

Fig 2. Distribution of CL-K1 serum levels (median values) among the study groups (SEP: diagnosed with S. haematobium egg in urine; SELP: Negative for S. haematobium egg in urine but positive for anti-schistosoma total IgG; SELN: Negative for S. haematobium egg and anti-schistosoma total IgG).

P = 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, P<0.001; SEP vs. SELP+SELN, P>0.05). Numbers in parentheses indicates absolute counts of sample size in each group.

Fig 3. Distribution of CL-K1 serum levels (median values) with investigated rs7567833G/A (p.R216H) variant.

(Left) SELN group (Right): SELP+SELN group. P = 0.03 and P = 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, P<0.05; SELN-GA vs. SELN-AA, P>0.05); (SELN+SELP-GG vs. SELN+SELP-AA, P<0.01; SELN+SELP-GA vs. SELN+SELP-AA, P<0.05). Numbers in parentheses indicates absolute counts of sample size in each group. (SEP: diagnosed with S. haematobium egg in urine; SELP: Negative for S. haematobium egg in urine but positive for anti-schistosoma total IgG; SELN: Negative for S. haematobium egg and anti-schistosoma total IgG).

Fig 4. Distribution of CL-K1 serum levels (median values) with investigated COLEC11 haplotypes (Left) SELN controls (Right): SELP+SELN combined controls.

P = 0.03 and P = 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 (COLEC11*TCCG-SELN vs. COLEC11*TCCA-SELN, P<0.05; COLEC11*CCCG-SELN vs. COLEC11*TCCA-SELN, P>0.05; COLEC11*TCCG-SELN+SELP vs. COLEC11*TCCA-SELN+SELP, P<0.001; COLEC11*TCCG-SELN+SELP vs. COLEC11*CCCG-SELN+SELP, P>0.05). Numbers in parentheses indicate absolute counts of sample size in each group. SEP: diagnosed with S. haematobium egg in urine; SELP: Negative for S. haematobium egg in urine but positive for anti-schistosoma total IgG; SELN: Negative for S. haematobium egg and anti-schistosoma total IgG).

Fig 5. Distribution of CL-K1 serum levels (median values) with investigated COLEC11*TCCA haplotype in all study groups.

P<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 (COLEC11*TCCA-SEP vs. COLEC11*TCCA-SELN, P<0.001; COLEC11*TCCA-SEP vs. COLEC11*TCCA-SELP+SELN, P<0.01). Numbers in parentheses indicates absolute counts of sample size in each group. SEP: diagnosed with S. haematobium egg in urine; SELP: Negative for S. haematobium egg in urine but positive for anti-schistosoma total IgG; SELN: Negative for S. haematobium egg and anti-schistosoma total IgG.