Immunomodulatory effects of tick saliva on dermal cells exposed to Borrelia burgdorferi, the agent of Lyme disease
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 go...
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| Veröffentlicht in: | Parasites & vectors 2016-07, Vol.9 (1), p.394, Article 394 |
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| creator | Scholl, Dorothy C Embers, Monica E Caskey, John R Kaushal, Deepak Mather, Thomas N Buck, Wayne R Morici, Lisa A Philipp, Mario T |
| description | 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.
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.
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.
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. |
| doi_str_mv | 10.1186/s13071-016-1638-7 |
| format | Article |
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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.
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.
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.</description><identifier>ISSN: 1756-3305</identifier><identifier>EISSN: 1756-3305</identifier><identifier>DOI: 10.1186/s13071-016-1638-7</identifier><identifier>PMID: 27391120</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Animals ; Borrelia ; Borrelia burgdorferi - immunology ; Cells, Cultured ; Fibroblasts - drug effects ; Fibroblasts - immunology ; Fibroblasts - microbiology ; Gene Expression Profiling ; Health aspects ; Histocytochemistry ; Humans ; Immune response ; Immunologic Factors - metabolism ; Macaca mulatta ; Monocytes - drug effects ; Monocytes - immunology ; Monocytes - microbiology ; Observations ; Properties ; Rabbits ; Saliva ; Saliva - metabolism ; Salivary glands ; secretions ; Skin - microbiology ; Skin - pathology ; Tick Bites - immunology ; Ticks</subject><ispartof>Parasites & vectors, 2016-07, Vol.9 (1), p.394, Article 394</ispartof><rights>COPYRIGHT 2016 BioMed Central Ltd.</rights><rights>Copyright BioMed Central 2016</rights><rights>The Author(s). 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c528t-70f8e28dd1d7db564c0906c79087c5047d8c025df082f524f8a34d217f108a093</citedby><cites>FETCH-LOGICAL-c528t-70f8e28dd1d7db564c0906c79087c5047d8c025df082f524f8a34d217f108a093</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4938952/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4938952/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27391120$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Scholl, Dorothy C</creatorcontrib><creatorcontrib>Embers, Monica E</creatorcontrib><creatorcontrib>Caskey, John R</creatorcontrib><creatorcontrib>Kaushal, Deepak</creatorcontrib><creatorcontrib>Mather, Thomas N</creatorcontrib><creatorcontrib>Buck, Wayne R</creatorcontrib><creatorcontrib>Morici, Lisa A</creatorcontrib><creatorcontrib>Philipp, Mario T</creatorcontrib><title>Immunomodulatory effects of tick saliva on dermal cells exposed to Borrelia burgdorferi, the agent of Lyme disease</title><title>Parasites & vectors</title><addtitle>Parasit Vectors</addtitle><description>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.
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.
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.
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.</description><subject>Animals</subject><subject>Borrelia</subject><subject>Borrelia burgdorferi - immunology</subject><subject>Cells, Cultured</subject><subject>Fibroblasts - drug effects</subject><subject>Fibroblasts - immunology</subject><subject>Fibroblasts - microbiology</subject><subject>Gene Expression Profiling</subject><subject>Health aspects</subject><subject>Histocytochemistry</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immunologic Factors - metabolism</subject><subject>Macaca mulatta</subject><subject>Monocytes - drug effects</subject><subject>Monocytes - immunology</subject><subject>Monocytes - microbiology</subject><subject>Observations</subject><subject>Properties</subject><subject>Rabbits</subject><subject>Saliva</subject><subject>Saliva - metabolism</subject><subject>Salivary glands</subject><subject>secretions</subject><subject>Skin - microbiology</subject><subject>Skin - pathology</subject><subject>Tick Bites - immunology</subject><subject>Ticks</subject><issn>1756-3305</issn><issn>1756-3305</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNptkl1rFDEUhoMotlZ_gDcS8Epw6snMZJK5EWrxY2FB8OM6ZJOTaerMZE0ypfvvzbK1dkFykXDyvC_nHF5CXjI4Z0x27xJrQLAKWFexrpGVeEROmeBd1TTAHz94n5BnKV0DdNDz7ik5qUXTM1bDKYmraVrmMAW7jDqHuKPoHJqcaHA0e_OLJj36G03DTC3GSY_U4DgmirfbkNDSHOiHECOOXtPNEgcbosPo39J8hVQPOOe903o3IbU-oU74nDxxekz44u4-Iz8_ffxx-aVaf_28urxYV4bXMlcCnMRaWsussBvetQZ66IzoQQrDoRVWGqi5dSBrx-vWSd20tmbCMZAa-uaMvD_4bpfNhNaUVqIe1Tb6ScedCtqr45_ZX6kh3Ki2b2TP62Lw-s4ght8LpqyuwxLn0rNiEkTPe9Gyf9SgR1R-dqGYmcknoy7aTkrJJUChzv9DlWNx8ibM6HypHwneHAkKk_E2D3pJSa2-fztm2YE1MaQU0d0PyUDtk6IOSVElKWqfFCWK5tXD7dwr_kaj-QOdFrh-</recordid><startdate>20160708</startdate><enddate>20160708</enddate><creator>Scholl, Dorothy C</creator><creator>Embers, Monica E</creator><creator>Caskey, John R</creator><creator>Kaushal, Deepak</creator><creator>Mather, Thomas N</creator><creator>Buck, Wayne R</creator><creator>Morici, Lisa A</creator><creator>Philipp, Mario T</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISR</scope><scope>3V.</scope><scope>7SN</scope><scope>7SS</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>F1W</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H95</scope><scope>K9.</scope><scope>L.G</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20160708</creationdate><title>Immunomodulatory effects of tick saliva on dermal cells exposed to Borrelia burgdorferi, the agent of Lyme disease</title><author>Scholl, Dorothy C ; 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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.
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.
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.
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.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>27391120</pmid><doi>10.1186/s13071-016-1638-7</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Borrelia Borrelia burgdorferi - immunology Cells, Cultured Fibroblasts - drug effects Fibroblasts - immunology Fibroblasts - microbiology Gene Expression Profiling Health aspects Histocytochemistry Humans Immune response Immunologic Factors - metabolism Macaca mulatta Monocytes - drug effects Monocytes - immunology Monocytes - microbiology Observations Properties Rabbits Saliva Saliva - metabolism Salivary glands secretions Skin - microbiology Skin - pathology Tick Bites - immunology Ticks |
| title | Immunomodulatory effects of tick saliva on dermal cells exposed to Borrelia burgdorferi, the agent of Lyme disease |
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