Association between Toll-Like Receptor 4 (Thr399Ile and Asp299Gly), Toll-Like Receptor 2 196-174 Deletion Polymorphisms with cryptosporidiosis

Abstract

Toll-like receptors (TLRs) 2 and 4 specifically recognize lipopolysaccharide motifs on surfaces of microorganisms. Polymorphims in the TLR genes result in structural variations in the proteins, abnormal host-pathogen interactions and hence, altered immune response. Opportunistic parasite Cryptosporidium spp. infects immunocompromised patients who present with heterogeneous clinical manifestations ranging from mild infection resolving in a few weeks, to severe form characterized by voluminous diarrhoea, prolonged symptoms and recurrences. The present study investigates the role of TLR2 196_174del, TLR4 Asp299Gly and Thr399Ile polymorphisms in pathogenesis of cryptosporidiosis. Stool samples were collected from 210 immuno-compromised (renal transplant recipients and patients with Human immunodeficiency virus infection) both with and without cryptosporidiosis, and 200 healthy subjects for detection of Cryptosporidium spp. Blood samples were also collected from the patients and healthy subjects for genotyping of Δ22 (TLR2 196_174del) polymorphism, A896G (TLR4 Asp299Gly) and C1196T (Thr399Ile) single nucleotide polymorphisms (SNPs) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Cryptosporidium spp. was detected in 70 immunocompromised patients, while it was absent in all the healthy controls. No significant difference was observed in Δ22, A896G and C1196T alleles and genotypes (P > 0.05), between cases and controls. Thus, TLR2 196_174del, TLR4 Asp299Gly and Thr399Ile polymorphisms are not significantly associated with the pathogenesis or progression of cryptosporidiosis, in the Indian population included in the study.