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

Justin S Antony,Peter G Kremsner,Thirumalaisamy P Velavan,Olusola Ojurongbe,William Evan Secor

doi:10.1371/journal.pntd.0003647

Abstract

BackgroundUrinary 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 FindingsWe 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 (Pcorr = 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, Pcorr = 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, Pcorr = 0.0001).ConclusionsIn 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.

Highlights

Urogenital schistosomiasis, which is caused by infection with the trematode Schistosoma haematobium, is a major public health problem in sub-Saharan Africa (SSA)
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
We have previously shown that the lectin proteins mannose binding lectin (MBL) and MBL-associated serine protease 1 (MASP-1) and MASP-2 interact with schistosomal glycoconjugates, and subsequently activate the lectin complement cascade [19]

Summary

Introduction

Urogenital schistosomiasis, which is caused by infection with the trematode Schistosoma haematobium, is a major public health problem in sub-Saharan Africa (SSA). The incidence of S. haematobium infections in SSA, is most likely underreported and might be much higher [3]. Urinary schistosomiasis is endemic in Nigeria and approximately 25 million people are currently infected, with an estimated 101 million at risk [7]. Schistosomiasis can increase the risk of urinary tract infections and bladder cancer [8,9,10]. Children and early adolescents are at high risk of infection as their daily activities regularly include contact with water infested with infectious cercariae [11]. Urinary Schistosomiasis is a neglected tropical disease endemic in many sub Saharan -African countries. Schistosome teguments are fucosylated and CL-K1 has, through its collagen-like domain, a high binding affinity to fucose

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Results

Conclusion