Proinflammatory Cytokine Gene Expression by Murine Macrophages in Response toBrugia malayi WolbachiaSurface Protein

Chantima Porksakorn,Kiwon Park,Surang Nuchprayoon,Alan L Scott

doi:10.1155/2007/84318

Abstract

Wolbachia, an endosymbiotic bacterium found in most species of filarial parasites, is thought to play a significant role in inducing innate inflammatory responses in lymphatic filariasis patients. However, the Wolbachia-derived molecules that are recognized by the innate immune system have not yet been identified. In this study, we exposed the murine macrophage cell line RAW 264.7 to a recombinant form of the major Wolbachia surface protein (rWSP) to determine if WSP is capable of innately inducing cytokine transcription. Interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF) mRNAs were all upregulated by the rWSP stimulation in a dose-dependant manner. TNF transcription peaked at 3 hours, whereas IL-1β and IL-6 transcription peaked at 6 hours post-rWSP exposure. The levels of innate cytokine expression induced by a high-dose (9.0 μg/mL) rWSP in the RAW 264.7 cells were comparable to the levels induced by 0.1 μg/mL E. coli-derived lipopolysaccharides. Pretreatment of the rWSP with proteinase-K drastically reduced IL-1β, IL-6, and TNF transcription. However, the proinflammatory response was not inhibited by polymyxin B treatment. These results strongly suggest that the major Wolbachia surface protein molecule WSP is an important inducer of innate immune responses during filarial infections.

Highlights

Lymphatic filariasis remains a major debilitating and disfiguring disease that affects approximately 120 million people worldwide [1]
The drug-induced adverse reactions are associated with the increased post-treatment concentrations of proinflammatory cytokines and immune modulators, including tumor necrosis factor (TNF), interleukin (IL)-6, IL-10, lipopolysaccharide-binding protein (LBP), and soluble TNF receptors [12,13,14]
We report that a recombinant form of the with rWSP (WSP) from the B. malayi Wolbachia is a potent elicitor of the transcription of proinflammatory cytokines in murine macrophage cell line RAW 264.7

Summary

Introduction

Lymphatic filariasis remains a major debilitating and disfiguring disease that affects approximately 120 million people worldwide [1]. Host immune responses are thought to be a major factor contributing to disease progression in lymphatic filariasis, which manifests as either acute or chronic inflammation [8,9,10]. The adverse reactions associated with chemotherapeutic treatment are thought to be due to inflammatory responses directly induced by molecules liberated from drug-damaged microfilariae [1, 11]. The drug-induced adverse reactions are associated with the increased post-treatment concentrations of proinflammatory cytokines and immune modulators, including tumor necrosis factor (TNF), interleukin (IL)-6, IL-10, lipopolysaccharide-binding protein (LBP), and soluble TNF receptors (sTNF-Rs) [12,13,14]. It is believed that innate immune responses play a major role in this immune-mediated pathology, the nature of the parasitederived molecules that mediate this pathogenesis has not been defined

Methods

Results

Conclusion