Abstract
BackgroundThe prolonged feeding process 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 responses, which may be beneficial to spirochete transmission. The primary goal of this study was to test the hypothesis that tick saliva, in the context of Borrelia burgdorferi, can have widespread effects on the production of immune mediators in skin.MethodsA cross-section of tick feeding on skin was examined histologically. Human THP-1 cells stimulated with B. burgdorferi and grown in the presence or absence of tick saliva were examined by human DNA microarray, cytokine bead array, sandwich ELISA, and qRT-PCR. Similar experiments were also conducted using dermal fibroblasts.ResultsTick feeding on skin showed dermal infiltration of histiocytes and granulocytes at the bite location. Changes in monocytic transcript levels during co-culture with B. burgdorferi and saliva indicated that tick saliva had a suppressive effect on the expression of certain pro-inflammatory mediators, such as IL-8 (CXCL8) and TLR2, but had a stimulatory effect on specific molecules such as the Interleukin 10 receptor, alpha subunit (IL-10RA), a known mediator of the immunosuppressive signal of IL-10. Stimulated cell culture supernatants were analyzed via antigen-capture ELISA and cytokine bead array for inflammatory mediator production. Treatment of monocytes with saliva significantly reduced the expression of several key mediators including IL-6, IL-8 and TNF-alpha. Tick saliva had an opposite effect on dermal fibroblasts. Rather than inhibiting, saliva enhanced production of pro-inflammatory mediators, including IL-8 and IL-6 from these sentinel skin cells.ConclusionsThe effects of ixodid tick saliva on resident skin cells is cell type-dependent. The response to both tick and pathogen at the site of feeding favors pathogen transmission, but may not be wholly suppressed by tick saliva.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1638-7) contains supplementary material, which is available to authorized users.
Highlights
The prolonged feeding process of ixodid ticks, in combination with bacterial transmission, should lead to a robust inflammatory response at the blood-feeding site
Skin damage and inflammation is evident during tick feeding While tick saliva is known to suppress multiple mediators of immunity, as outlined in the Background section, it does not shut down inflammation at the site of the tick bite
The infiltration of cells includes a significant population of histiocytes, indicating that the monocyte/macrophage is a relevant cell population for analysis of the impact of tick saliva on the response to B. burgdorferi
Summary
The prolonged feeding process of ixodid ticks, in combination with bacterial transmission, should lead to a robust inflammatory response at the blood-feeding site. Vector-borne infectious diseases such as Lyme borreliosis (LB) result from complex interactions among three major components: host (mammal), pathogen (Borrelia burgdorferi (sensu lato)) and vector (Ixodes spp. ticks). The spirochete that causes LB, is transmitted during the feeding of infected Ixodes ticks. It has been shown that events at the tick-host interface are so complex that successful transmission of pathogens often depends on the immunosuppression of host responses, and on the enhancement of expression of certain vector genes [9, 10]. The enhancement of such genes is often mediated by the pathogen as exemplified by the B. burgdorferi-induced expression of two Ixodes scapularis genes, TROSPA (tick receptor for OspA) and Salp15 [9]. The establishment of B. burgdorferi infection, would not be possible without the enhanced expression of Salp by the tick
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