Role of Toll like Receptors and Mannose Binding Lectins in Innate Immune Response to Cryptosporidiosis

Farzana Begum, L (2014) Role of Toll like Receptors and Mannose Binding Lectins in Innate Immune Response to Cryptosporidiosis. Doctoral thesis, The Tamilnadu Dr.M.G.R. Medical University, Chennai.

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Abstract

Cryptosporidium spp. is as an important cause of parasitic diarrhea particularly among young children in developing countries. Studies from developing countries suggest that both asymptomatic and symptomatic cryptosporidial infections have a significant adverse effect on nutritional status and cognitive development of children. However, the mechanisms of innate immune response that serves as a first line of defense in cryptosporidial infection are not completely understood. These in vitro and genetic studies provide preliminary data on the role of TLRs and MBL in innate immune response to cryptosporidial infection. 1. The in vitro study showed that Caco2, an intestinal epithelial cell line was a suitable cell culture model to establish C. parvum infection and to study TLR mediated immune response. Upregulation of both TLR2 and TLR4 was observed in Caoc2 cells infected with C. parvum sporozoites. The reporter gene assay showed NF-ḱB translocation at 12 hours post C. parvum infection which could be a downstream result of TLR signaling. The supernatants of infected Caco-2 cells produced IL-8 at 12 hours, which increased exponentially till 48 hours post-infection. Presence of low IFN-γ at the end of 24 hours could be interpreted as a limited role of NK cells and other IEL as a source. 2. In the TLR genetic susceptibility study, an increased frequency of genotypes AG and GG of the TLR4 SNP, rs4986790 was observed among controls, suggesting a protective effect. 3. Among the MBL2 genotypes, the structural variant allele ‘B’ at codon 54 of exon 1 was significantly higher in cases than controls. Haplotype analysis showed that homozygous X/O was associated with increased risk of cryptosporidiosis. A cut off of 873.5ng/ml of plasma MBL was established to define ‘MBL deficiency’ and the deficiency was seen more often among cases than controls. 4. Serum MBL levels assessed before and after the first episode of cryptosporidial diarrhea in cases showed a decline possibly due to utilization for complement fixation and did not correlate with both promoter and codon SNPs of MBL2. In conclusion, in vitro studies will help in understating the TLR pathway, identifying potential cryptosporidial ligands and developing mucosal adjuvant vaccines for cryptosporidial infections. The in vivo genetic susceptibility studies may identify risk groups for novel therapeutic intervention or prevention of cryptosporidial diarrhea.

Item Type: Thesis (Doctoral)
Uncontrolled Keywords: Toll like Receptors, Mannose Binding Lectins, Innate Immune Response, Cryptosporidiosis.
Subjects: MEDICAL > Gastroenterology
Depositing User: Subramani R
Date Deposited: 11 Jan 2022 02:17
Last Modified: 11 Jan 2022 02:17
URI: http://repository-tnmgrmu.ac.in/id/eprint/13182

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