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Immunomodulatory effects of tick saliva on dermal cells exposed to Borrelia burgdorferi, the agent of Lyme disease.

Abstract：

BACKGROUND:The 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. METHODS:A 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. RESULTS:Tick 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. CONCLUSIONS:The 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.

journal_name

Parasit Vectors

journal_title

Parasites & vectors

authors

Scholl DC,Embers ME,Caskey JR,Kaushal D,Mather TN,Buck WR,Morici LA,Philipp MT

doi

10.1186/s13071-016-1638-7

subject

Has Abstract

pub_date

2016-07-08 00:00:00

pages

394

issue

issn

1756-3305

pii

10.1186/s13071-016-1638-7

journal_volume

pub_type

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Immunomodulatory effects of tick saliva on dermal cells exposed to Borrelia burgdorferi, the agent of Lyme disease.