Amblyomma americanum serpin 27 (AAS27) is a tick salivary anti-inflammatory protein secreted into the host during feeding

Detalhes bibliográficos
Autor(a) principal: Tirloni, Lucas
Data de Publicação: 2019
Outros Autores: Kim, Tae Kwon, Oliveira, Markus Berger, Termignoni, Carlos, Vaz Junior, Itabajara da Silva, Mulenga, Albert
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UFRGS
Texto Completo: http://hdl.handle.net/10183/199733
Resumo: Ticks successfully feed and transmit pathogens by injecting pharmacological compounds in saliva to thwart host defenses. We have previously used LC-MS/MS to identify proteins that are present in saliva of unfed Amblyomma americanum ticks that were exposed to different hosts. Here we show that A. americanum serine protease inhibitor (serpin) 27 (AAS27) is an immunogenic saliva protein that is injected into the host within the first day of tick feeding and is an anti-inflammatory protein that might act by blocking plasmin and trypsin functions. Although AAS27 is injected into the host throughout tick feeding, qRT-PCR and western blotting analyses indicate that the respective transcript and protein are present in high amounts within the first 24 h of tick feeding. Biochemical screening of Pichia pastoris-expressed recombinant (r) AAS27 against mammalian proteases related to host defense shows it is an inhibitor of trypsin and plasmin, with stoichiometry of inhibition indices of 3.5 and 3.8, respectively. Consistent with typical inhibitory serpins, rAAS27 formed heat- and SDS-stable irreversible complexes with both proteases. We further demonstrate that rAAS27 inhibits trypsin with ka of 6.46 ± 1.24 x 104 M-1 s-1, comparable to serpins of other tick species. We show that native AAS27 is part of the repertoire of proteins responsible for the inhibitory activity against trypsin in crude tick saliva. AAS27 is likely utilized by the tick to evade the hosts inflammation defense since rAAS27 blocks both formalin and compound 48/80-induced inflammation in rats. Tick immune sera of rabbits that had acquired resistance against tick feeding following repeated infestations with A. americanum or Ixodes scapularis ticks reacts with rAAS27. Of significant interest, antibody to rAAS27 blocks this serpin inhibitory functions. Taken together, we conclude that AAS27 is an anti-inflammatory protein secreted into the host during feeding and may represent a potential candidate for development of an anti-tick vaccine.
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spelling Tirloni, LucasKim, Tae KwonOliveira, Markus BergerTermignoni, CarlosVaz Junior, Itabajara da SilvaMulenga, Albert2019-09-25T03:45:14Z2019http://hdl.handle.net/10183/199733001101948Ticks successfully feed and transmit pathogens by injecting pharmacological compounds in saliva to thwart host defenses. We have previously used LC-MS/MS to identify proteins that are present in saliva of unfed Amblyomma americanum ticks that were exposed to different hosts. Here we show that A. americanum serine protease inhibitor (serpin) 27 (AAS27) is an immunogenic saliva protein that is injected into the host within the first day of tick feeding and is an anti-inflammatory protein that might act by blocking plasmin and trypsin functions. Although AAS27 is injected into the host throughout tick feeding, qRT-PCR and western blotting analyses indicate that the respective transcript and protein are present in high amounts within the first 24 h of tick feeding. Biochemical screening of Pichia pastoris-expressed recombinant (r) AAS27 against mammalian proteases related to host defense shows it is an inhibitor of trypsin and plasmin, with stoichiometry of inhibition indices of 3.5 and 3.8, respectively. Consistent with typical inhibitory serpins, rAAS27 formed heat- and SDS-stable irreversible complexes with both proteases. We further demonstrate that rAAS27 inhibits trypsin with ka of 6.46 ± 1.24 x 104 M-1 s-1, comparable to serpins of other tick species. We show that native AAS27 is part of the repertoire of proteins responsible for the inhibitory activity against trypsin in crude tick saliva. AAS27 is likely utilized by the tick to evade the hosts inflammation defense since rAAS27 blocks both formalin and compound 48/80-induced inflammation in rats. Tick immune sera of rabbits that had acquired resistance against tick feeding following repeated infestations with A. americanum or Ixodes scapularis ticks reacts with rAAS27. Of significant interest, antibody to rAAS27 blocks this serpin inhibitory functions. Taken together, we conclude that AAS27 is an anti-inflammatory protein secreted into the host during feeding and may represent a potential candidate for development of an anti-tick vaccine.application/pdfengPLOS Neglected Tropical Diseases. San Francisco, CA. Vol. 13, no. 8 (Aug. 2019), e0007660, 27 p.SerpinasProteínas e peptídeos salivaresAnti-inflamatóriosAmblyomma americanumAmblyomma americanum serpin 27 (AAS27) is a tick salivary anti-inflammatory protein secreted into the host during feedingEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001101948.pdf.txt001101948.pdf.txtExtracted Texttext/plain88969http://www.lume.ufrgs.br/bitstream/10183/199733/2/001101948.pdf.txt61ee979cbe58b1e382f9a7b1cfe6e5ddMD52ORIGINAL001101948.pdfTexto completo (inglês)application/pdf2843372http://www.lume.ufrgs.br/bitstream/10183/199733/1/001101948.pdf61d6e6764bbc8a3650fffbd003303dedMD5110183/1997332021-11-21 05:26:43.14596oai:www.lume.ufrgs.br:10183/199733Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2021-11-21T07:26:43Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false
dc.title.pt_BR.fl_str_mv Amblyomma americanum serpin 27 (AAS27) is a tick salivary anti-inflammatory protein secreted into the host during feeding
title Amblyomma americanum serpin 27 (AAS27) is a tick salivary anti-inflammatory protein secreted into the host during feeding
spellingShingle Amblyomma americanum serpin 27 (AAS27) is a tick salivary anti-inflammatory protein secreted into the host during feeding
Tirloni, Lucas
Serpinas
Proteínas e peptídeos salivares
Anti-inflamatórios
Amblyomma americanum
title_short Amblyomma americanum serpin 27 (AAS27) is a tick salivary anti-inflammatory protein secreted into the host during feeding
title_full Amblyomma americanum serpin 27 (AAS27) is a tick salivary anti-inflammatory protein secreted into the host during feeding
title_fullStr Amblyomma americanum serpin 27 (AAS27) is a tick salivary anti-inflammatory protein secreted into the host during feeding
title_full_unstemmed Amblyomma americanum serpin 27 (AAS27) is a tick salivary anti-inflammatory protein secreted into the host during feeding
title_sort Amblyomma americanum serpin 27 (AAS27) is a tick salivary anti-inflammatory protein secreted into the host during feeding
author Tirloni, Lucas
author_facet Tirloni, Lucas
Kim, Tae Kwon
Oliveira, Markus Berger
Termignoni, Carlos
Vaz Junior, Itabajara da Silva
Mulenga, Albert
author_role author
author2 Kim, Tae Kwon
Oliveira, Markus Berger
Termignoni, Carlos
Vaz Junior, Itabajara da Silva
Mulenga, Albert
author2_role author
author
author
author
author
dc.contributor.author.fl_str_mv Tirloni, Lucas
Kim, Tae Kwon
Oliveira, Markus Berger
Termignoni, Carlos
Vaz Junior, Itabajara da Silva
Mulenga, Albert
dc.subject.por.fl_str_mv Serpinas
Proteínas e peptídeos salivares
Anti-inflamatórios
Amblyomma americanum
topic Serpinas
Proteínas e peptídeos salivares
Anti-inflamatórios
Amblyomma americanum
description Ticks successfully feed and transmit pathogens by injecting pharmacological compounds in saliva to thwart host defenses. We have previously used LC-MS/MS to identify proteins that are present in saliva of unfed Amblyomma americanum ticks that were exposed to different hosts. Here we show that A. americanum serine protease inhibitor (serpin) 27 (AAS27) is an immunogenic saliva protein that is injected into the host within the first day of tick feeding and is an anti-inflammatory protein that might act by blocking plasmin and trypsin functions. Although AAS27 is injected into the host throughout tick feeding, qRT-PCR and western blotting analyses indicate that the respective transcript and protein are present in high amounts within the first 24 h of tick feeding. Biochemical screening of Pichia pastoris-expressed recombinant (r) AAS27 against mammalian proteases related to host defense shows it is an inhibitor of trypsin and plasmin, with stoichiometry of inhibition indices of 3.5 and 3.8, respectively. Consistent with typical inhibitory serpins, rAAS27 formed heat- and SDS-stable irreversible complexes with both proteases. We further demonstrate that rAAS27 inhibits trypsin with ka of 6.46 ± 1.24 x 104 M-1 s-1, comparable to serpins of other tick species. We show that native AAS27 is part of the repertoire of proteins responsible for the inhibitory activity against trypsin in crude tick saliva. AAS27 is likely utilized by the tick to evade the hosts inflammation defense since rAAS27 blocks both formalin and compound 48/80-induced inflammation in rats. Tick immune sera of rabbits that had acquired resistance against tick feeding following repeated infestations with A. americanum or Ixodes scapularis ticks reacts with rAAS27. Of significant interest, antibody to rAAS27 blocks this serpin inhibitory functions. Taken together, we conclude that AAS27 is an anti-inflammatory protein secreted into the host during feeding and may represent a potential candidate for development of an anti-tick vaccine.
publishDate 2019
dc.date.accessioned.fl_str_mv 2019-09-25T03:45:14Z
dc.date.issued.fl_str_mv 2019
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dc.language.iso.fl_str_mv eng
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dc.relation.ispartof.pt_BR.fl_str_mv PLOS Neglected Tropical Diseases. San Francisco, CA. Vol. 13, no. 8 (Aug. 2019), e0007660, 27 p.
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