Thesis Abstract

Abstract
Lymphatic filariasis caused by Wuchereria bancrofti is a debilitating disease affecting millions of people in tropical and subtropical regions. The immune response to the parasite plays a crucial role in the pathogenesis of the disease. Kolaviron, a natural biflavonoid complex extracted from Garcinia kola seeds, has been shown to possess various biological activities including antioxidant and anti-inflammatory properties. In this study, we investigated the effects of kolaviron on lymphocytes proliferation, expression of toll-like receptor-2 (TLR-2), and vascular endothelial growth factor-C (VEGF-C) genes in W. bancrofti infected blood. Peripheral blood samples were collected from individuals infected with W. bancrofti, and lymphocytes were isolated and cultured in the presence or absence of kolaviron. Cell proliferation was assessed using MTT assay, and gene expression levels of TLR-2 and VEGF-C were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Our results showed that kolaviron treatment significantly inhibited lymphocyte proliferation in a dose-dependent manner. Furthermore, kolaviron downregulated the expression of TLR-2 and VEGF-C genes in W. bancrofti infected lymphocytes compared to untreated cells. The modulation of TLR-2 expression by kolaviron suggests a potential mechanism by which this natural compound may exert its immunomodulatory effects in lymphatic filariasis. TLR-2 is known to play a crucial role in the recognition of microbial pathogens and activation of innate immune responses. By downregulating TLR-2 expression, kolaviron may dampen the inflammatory response associated with W. bancrofti infection, thereby reducing tissue damage and disease progression. Additionally, the suppression of VEGF-C expression by kolaviron highlights its potential anti-lymphangiogenic effects, which could help in inhibiting the formation of new lymphatic vessels and limiting the spread of the parasite. Overall, our findings suggest that kolaviron has the ability to modulate lymphocyte proliferation and gene expression in W. bancrofti infected blood. Further studies are warranted to elucidate the detailed mechanisms underlying the immunomodulatory effects of kolaviron and its potential as a therapeutic agent for lymphatic filariasis.

Thesis Overview

1.0 INTRODUCTION

Lymphatic filariasis, caused by parasitic Wuchereria bancrofti, is a mosquito borne disease characterized by a broad spectrum of clinical manifestation such as temporal/permanent disability and disfiguring leading to severe damage and painful swellings (lymphedema) of the legs and genitals in the late stage of the disease (Hoerauf et al., 2011; WHO, 2012; Gomase et al., 2013) and eventually stigmatization (WHO, 2013). Although the events leading to the development of chronic pathology in lymphatic filariasis are not fully understood, live filarial parasite and/or their products have a direct effect on lymphatic endothelial cells and in the cells of the innate and adaptive immune system (Nutman, 2013). Vascular endothelial growth factor (VEGF) family which is key regulators of endothelial cell functions has been implicated in lymphangiogenesis and angiogenesis in lymphatic pathology (Pfar et al., 2009). Their levels are significantly elevated in individuals with filarial infection both in chronic and microfilaremic states (Bennuru et al., 2010). The key mediators when it comes to complications associated with lymphatic filariasis are toll like receptors (TLR). They are pattern recognition factors of the innate immune system responsible for the microbial detection and initiation of the host immune response (Kawai and Akira, 2010). Wolbachia, a Gram negative endosymbiont in filarial parasites are key inducers of pro inflammatory cytokines which interact with the immune system through TLR2 thus, contributing to the pathology of lymphatic filariasis (Hise et al, 2007).