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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)-1 β , 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-1 β  and IL-6 transcription peaked at 6 hours post-rWSP exposure. The levels of innate cytokine expression induced by a high-dose (9.0  μ g/mL) rWSP in the RAW 264.7 cells were comparable to the levels induced by 0.1  μ g/mL  E. coli -derived lipopolysaccharides. Pretreatment of the rWSP with  proteinase-K drastically reduced IL-1 β , 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.

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