Project Abstract

Abstract
Wuchereria bancrofti is a parasitic nematode responsible for lymphatic filariasis, a debilitating disease affecting millions worldwide. In this study, we investigated the effects of kolaviron, a natural antioxidant derived from Garcinia kola seeds, on lymphocyte proliferation and the 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 with microfilaremia and divided into four groups untreated infected, treated infected with kolaviron, treated uninfected with kolaviron, and healthy controls. Lymphocytes were isolated and cultured in the presence of kolaviron, and proliferation was measured using MTT assay. The expression levels of TLR-2 and VEGF-C genes were assessed by quantitative real-time PCR. Our results showed a significant increase in lymphocyte proliferation in the treated infected group compared to the untreated infected group. Kolaviron treatment also led to a downregulation of TLR-2 expression in infected lymphocytes, suggesting a potential role in modulating the host immune response to W. bancrofti infection. Furthermore, VEGF-C gene expression was significantly reduced in the treated infected group compared to the untreated infected group, indicating a possible anti-lymphangiogenic effect of kolaviron in the context of lymphatic filariasis. Overall, our findings suggest that kolaviron has immunomodulatory effects on lymphocyte proliferation and gene expression in W. bancrofti infected blood. These results provide valuable insights into the potential use of kolaviron as an adjunct therapy for lymphatic filariasis, by targeting host immune responses and lymphangiogenesis pathways. Further studies are warranted to elucidate the underlying mechanisms of kolaviron action and its therapeutic potential in the context of parasitic infections like W. bancrofti.

Project 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).