Cloning and characterization of high mobility group box protein 1 (HMGB1) of Wuchereria bancrofti and Brugia malayi

Sivasakthivel Thirugnanam,Kalyanasundaram Ramaswamy,Gajalakshmi Dakshinamoorthy,Gnanasekar Munirathinam,Maryada V Reddy,Anandharaman Veerapathran

doi:10.1007/s00436-012-2878-x

Abstract

A human homologue of high mobility group box 1 (HMGB1) protein was cloned and characterized from the human filarial parasites Wuchereria bancrofti and Brugia malayi. Sequence analysis showed that W. bancrofti HMGB1 (WbHMGB1) and B. malayi HMGB1 (BmHMGB1) proteins share 99 % sequence identity. Filarial HMGB1 showed typical architectural sequence characteristics of HMGB family of proteins and consisted of only a single HMG box domain that had significant sequence similarity to the pro-inflammatory B box domain of human HMGB1. When incubated with mouse peritoneal macrophages and human promyelocytic leukemia cells, rBmHMGB1 induced secretion of significant levels of pro-inflammatory cytokines such as TNF-α, GM-CSF, and IL-6. Functional analysis also showed that the filarial HMGB1 proteins can bind to supercoiled DNA similar to other HMG family of proteins. BmHMGB1 protein is expressed in the adult and microfilarial stages of the parasite and is found in the excretory secretions of the live parasites. These findings suggest that filarial HMGB1 may have a significant role in lymphatic pathology associated with lymphatic filariasis.

Highlights

Lymphatic filariasis is caused mainly by two parasitic worms, Wuchereria bancrofti and Brugia malayi
Sequence analysis showed that W. bancrofti HMGB1 (WbHMGB1) and B. malayi HMGB1 (BmHMGB1) proteins share 99 % identity and differed only in one amino acid which was present outside the High mobility group (HMG) box domain
Homologues of high mobility group box 1 (HMGB1) proteins are reported from protozoan and trematode parasites such as Plasmodium (Kumar et al 2008), Entamoeba (Abhyankar et al 2008), Trypanosoma (Morales et al 1992), Toxoplasma (Zhao et al 2009), and Schistosoma (Gnanasekar et al 2006)

Summary

Introduction

Lymphatic filariasis is caused mainly by two parasitic worms, Wuchereria bancrofti and Brugia malayi. Host inflammatory responses triggered by dead larvae and adult parasites in infected tissues are believed to be an important triggering mechanism in lymphatic filarial pathogenesis (Dreyer et al 2000; Taylor et al 2010). Several previous reports showed that Wolbachia, an intracellular symbiotic bacterium present in lymphatic filarial parasites, can induce inflammatory reactions in the host by activating immune cells including macrophages (Turner et al 2006; Taylor et al 2005; Brattig et al 2000, 2004). All studies to date attribute the inflammatory response associated with lymphatic filariasis to the endosymbiont Wolbachia (Taylor et al 2005)

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