TICK SALIVA INHIBITS INFLAMMATION IN MONOCYTES STIMULATED WITH B BURGDORFERI

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: The prolonged feeding of ixodid ticks, in combination with bacterial transmission should lead to a robust inflammatory response at the blood-feeding site. Yet, factors present in tick saliva may down-regulate such deleterious responses. To maintain feeding success, ticks require anti-inflammatory and immunosuppressive elements in their saliva. In the host, activated monocytes circulate throughout, distributing the effects of both pathogen and vector (tick saliva). These cells play important roles in immune defense and inflammation. Monocytes produce pro-inflammatory mediators such as IL-8, a chemokine that controls the influx of inflammatory and immune cells, and IL-6, a key B-cell differentiation factor. Hypothesis: Tick saliva, in the context of B. burgdorferi (Bb) transmission, can have widespread effects on the expression of inflammatory pathways associated with monocytes/macrophages. This study aims to identify the in vitro effects of tick saliva on human monocyte gene expression co-cultured with Bb. Methods: RNA transcripts isolated from Human THP-1 monocytes stimulated with Bb in the presence or absence of tick saliva, at four time points (30-min, 2-hr, 12-hr, and 24-hr) were used to profile global gene-expression, using human oligonucleotide arrays. Differential expresser's were identified based on significance (P equal to or less than 0.05) and magnitude (equal to or greater than 2-fold). Ingenuity Pathways Analysis was used to investigate the function, biological processes, pathways, and network interactions of the affected genes. Results: Saliva can have a suppressive effect on the expression of certain pro-inflammatory mediators, such as IL-8, as well as have a stimulatory effect on specific molecules such as IL-10RA, IL-4r, IL5r and the SOCS family. Conclusions: Microarray results can provide a broad perspective on monocytic metabolic pathways and families of genes affected by tick saliva during co-culture with Bb.