Research Article: Lectin Complement Protein Collectin 11 (CL-K1) and Susceptibility to Urinary Schistosomiasis

Date Published: March 25, 2015

Publisher: Public Library of Science

Author(s): Justin S. Antony, Olusola Ojurongbe, Peter G. Kremsner, Thirumalaisamy P. Velavan, William Evan Secor.

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.

Partial Text: Urogenital schistosomiasis, which is caused by infection with the trematode Schistosoma haematobium, is a major public health problem in sub-Saharan Africa (SSA). Of the more than 200 million cases reported worldwide, 93% occur in SSA [1]. Up to two-thirds of S. haematobium infections result in genital schistosomiasis [2]. The incidence of S. haematobium infections in SSA, however, is most likely underreported and might be much higher [3]. Schistosomiasis accounts for the loss of more than 70 million disability adjusted life years (DALYs) [4,5]. A large proportion of infected individuals experience hematuria (70 million), dysuria (32 million), bladder-wall pathology (18 million), and severe hydronephrosis (10 million) [6]. Urinary schistosomiasis is endemic in Nigeria and approximately 25 million people are currently infected, with an estimated 101 million at risk [7]. Schistosomiasis can also increase the risk of urinary tract infections and bladder cancer [8–10]. Children and early adolescents are at high risk of infection as their daily activities regularly include contact with water infested with infectious cercariae [11]. Limited access to praziquantel treatment for schistosomiasis, repeated re-exposure, and rapid reinfections all contribute to the disease burden [11,12].

Different immune strategies are employed by the host immune system to thwart an infection and the innate immune system plays a critical role in the clearance of some pathogens. Immune evasion from complement components is an important criterion for schistosomes to successfully establish an infection [14,39]. Lectin pathway proteins of the complement system are the first components to recognize the pathogen. These proteins can initiate a complement attack cascade independent of a specific antibody response [40]. Our previous studies have demonstrated that lectin proteins Ficolin-2 [37] and MBL [36] are involved in S. haematobium infections.



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