Association of Toll-like Receptor 9 (TLR9) Alterations in Malaria Susceptibility and Severity: A Tribal Population Based Study in the Malaria Endemic State of Assam, India

Background: Toll-like receptors (TLRs) are group of trans-membrane proteins that recognizes specific molecular pattern and activates the downstream cytokines for the efficient clearance of pathogens. Objectives: To evaluate the role of TLR9 1486T/C polymorphism and its association with the malarial pathogenicity and severity. Material and Methods: Present study was a cohort based study and a total number of 150 samples were drawn from three major tribal population group's viz., Karbi, Dimasa and Boro-Kachari. TLR9 (1486T/C) gene polymorphism was assessed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Differential TLR9 m-RNA expression was assessed using Real time PCR (RT-PCR). Results: TLR9 1486T/C genotype variant showed increased risk for the susceptibility of malarial infection (p= 0.141) compared to controls. The variant genotype showed significant increased risk with susceptibility to severe malaria infection (p=0.047) compared to uncomplicated malaria (UC-M). TLR9 mRNA level expression showed up-regulation in UC-M compared to controls. Decreased TLR9 expression was found in SM cases compared to UC-M (p=0.312). Significant down-regulation of TLR9 gene was found in UC-M with variant C genotype cases compared to wild types (p=0.039). Conclusion: Our finding indicates the association of the TLR9 gene polymorphism and linked differential expression modulation in the development of malarial pathogenicity.