This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Monocytes are important regulators of inflammation. They are able to produce pro-inflammatory mediators such as IL-8, a chemokine that controls the influx of mammalian inflammatory and immune cells to sites of injury and infection, and IL-6, a key B cell differentiation factor. The prolonged and tissue-damaging feeding process of ixodid ticks, in combination with bacterial transmission, should lead to a vigorous inflammatory response. However, it is believed that factors present in tick saliva may down-regulate such deleterious responses. We hypothesized that tick saliva would down-regulate pro-inflammatory mediators elicited in vitro from monocytes stimulated with B. burgdorferi. Methods: Cells of the human monocytic line THP-1 were seeded at an initial density of 5 x 105 /ml. Cells were stimulated with live B. burgdorferi strain B31-5A19 for 24 hours in the presence or absence of pilocarpine (PC)-induced I. scapularis saliva at 1:20 or 1:500 dilutions. Controls included PC-only treated cells. After stimulation, viability was assessed via Trypan Blue staining, and supernatants were harvested for IL-6, TNF-alpha, and IL-8 detection by antibody-sandwich ELISA. Results: Tick saliva (1:20) significantly inhibited production of IL-6, TNF-alpha, and IL-8 by THP-1 cells stimulated with B. burgdorferi when compared to B. burgdorferi-only treated cells. PC controls, at the final concentration present in tick saliva (0.7 M), as determined by HPLC, had no effect. Conclusion: We have provided proof of concept that tick saliva inhibits monocyte dependent inflammatory responses to B. burgdorferi.
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