Avaliação do papel da via de sinalização de TREM-1 na leishmaniose cutânea localizada (LCL) humana
Autor(a) principal: | |
---|---|
Data de Publicação: | 2019 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
Texto Completo: | https://www.arca.fiocruz.br/handle/icict/37358 |
Resumo: | Leishmaniasis remains one of the most neglected tropical diseases in the world. The immune response of the host against Leishmania plays a critical role in promoting parasite death and also promotes the severity of the disease. The Myeloid Cell Expression Receptor (TREM) has recently been identified as an immune response amplifier, which acts synergistically with Toll-like receptors (TLRs) in the production of pro-inflammatory mediators. TREM-1 is expressed strictly in myeloide lineage cells, mainly neutrophils. Its signaling form depends on the adaptive protein DAP12, which results in the activation of NFêB and the expression of reference genes, as well as in the degranulation, production of ROS and cytokines. OBJECTIVE: Based on this, the present study investigated the role of TREM-1 during L. braziliensis infection. MATERIAL AND METHODS: First, public transcriptome data of lesions from patients infected by L. braziliensis compared to not infected skin obtained from GEODataSets. After, the results were validated by real-time PCR with new samples. Finally, the mechanisms of activation of TREM-1 during human neutrophil infection in vitro were investigated. RESULTS: The transcriptome data analysis demonstrated an increase in TREM-1 expression, including all signaling molecules. These results were confirmed by RT-qPCR and immunohistochemistry in new samples. On the other hand, a negative correlation of messenger RNA of TREM-1, DAP12, TLR2 and TLR4 was observed on the circulating neutrophils of these patients. In addition, exposure to L. braziliensis increased the expression of TREM-1 on the surface of human neutrophils, leading to the degranulation of matrix metalloproteinase 9. Finally, TREM-1 and TLR2 are synergists in neutrophil degeneration but not in internalization of L brasiliensis. CONCLUSION: TREM-1 may be a potential target for modulation of inflammatory response in LCL, remaining the ability of neutrophil to kill Leishmania. |
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Ampuero, Mariana RosaPrates, Deboraci BritoCarvalho, Lucas Pedreira deTavares, Natália MachadoTavares, Natalia Machado2019-11-25T16:05:52Z2019-11-25T16:05:52Z2019AMPUERO, Mariana Rosa. Avaliação do papel da via de sinalização de TREM-1 na leishmaniose cutânea localizada (LCL) humana. 2019. 63 f. Dissertação (Mestrado em Patologia) – Universidade Federal da Bahia; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, 2019.https://www.arca.fiocruz.br/handle/icict/37358Leishmaniasis remains one of the most neglected tropical diseases in the world. The immune response of the host against Leishmania plays a critical role in promoting parasite death and also promotes the severity of the disease. The Myeloid Cell Expression Receptor (TREM) has recently been identified as an immune response amplifier, which acts synergistically with Toll-like receptors (TLRs) in the production of pro-inflammatory mediators. TREM-1 is expressed strictly in myeloide lineage cells, mainly neutrophils. Its signaling form depends on the adaptive protein DAP12, which results in the activation of NFêB and the expression of reference genes, as well as in the degranulation, production of ROS and cytokines. OBJECTIVE: Based on this, the present study investigated the role of TREM-1 during L. braziliensis infection. MATERIAL AND METHODS: First, public transcriptome data of lesions from patients infected by L. braziliensis compared to not infected skin obtained from GEODataSets. After, the results were validated by real-time PCR with new samples. Finally, the mechanisms of activation of TREM-1 during human neutrophil infection in vitro were investigated. RESULTS: The transcriptome data analysis demonstrated an increase in TREM-1 expression, including all signaling molecules. These results were confirmed by RT-qPCR and immunohistochemistry in new samples. On the other hand, a negative correlation of messenger RNA of TREM-1, DAP12, TLR2 and TLR4 was observed on the circulating neutrophils of these patients. In addition, exposure to L. braziliensis increased the expression of TREM-1 on the surface of human neutrophils, leading to the degranulation of matrix metalloproteinase 9. Finally, TREM-1 and TLR2 are synergists in neutrophil degeneration but not in internalization of L brasiliensis. CONCLUSION: TREM-1 may be a potential target for modulation of inflammatory response in LCL, remaining the ability of neutrophil to kill Leishmania.Leishmaniasis remains one of the most neglected tropical diseases in the world. The immune response of the host against Leishmania plays a critical role in promoting parasite death and also promotes the severity of the disease. The Myeloid Cell Expression Receptor (TREM) has recently been identified as an immune response amplifier, which acts synergistically with Toll-like receptors (TLRs) in the production of pro-inflammatory mediators. TREM-1 is expressed strictly in myeloide lineage cells, mainly neutrophils. Its signaling form depends on the adaptive protein DAP12, which results in the activation of NFκB and the expression of reference genes, as well as in the degranulation, production of ROS and cytokines. OBJECTIVE: Based on this, the present study investigated the role of TREM-1 during L. braziliensis infection. MATERIAL AND METHODS: First, public transcriptome data of lesions from patients infected by L. braziliensis compared to not infected skin obtained from GEODataSets. After, the results were validated by real-time PCR with new samples. Finally, the mechanisms of activation of TREM-1 during human neutrophil infection in vitro were investigated. RESULTS: The transcriptome data analysis demonstrated an increase in TREM-1 expression, including all signaling molecules. These results were confirmed by RT-qPCR and immunohistochemistry in new samples. On the other hand, a negative correlation of messenger RNA of TREM-1, DAP12, TLR2 and TLR4 was observed on the circulating neutrophils of these patients. In addition, exposure to L. braziliensis increased the expression of TREM-1 on the surface of human neutrophils, leading to the degranulation of matrix metalloproteinase 9. Finally, TREM-1 and TLR2 are synergists in neutrophil degeneration but not in internalization of L brasiliensis. CONCLUSION: TREM-1 may be a potential target for modulation of inflammatory response in LCL, remaining the ability of neutrophil to kill Leishmania.O presente trabalho foi realizado com apoio da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) – Código de Financiamento 001Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.porInstituto Gonçalo MonizLeishmania braziliensisLeishmania cutânea localizadaNeutrófilosCélulas mielóidesLeishmania braziliensisLocalized Cutaneous LeishmaniasisHuman neutrophilsMyeloid CellsAvaliação do papel da via de sinalização de TREM-1 na leishmaniose cutânea localizada (LCL) humanainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis2019Coordenação de EnsinoUniversidade Federal da Bahia. Faculdade de Medicina. Instituto Gonçalo MonizMestrado AcadêmicoSalvador/BAPós-Graduação em Patologiainfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txttext/plain1748https://www.arca.fiocruz.br/bitstream/icict/37358/1/license.txt8a4605be74aa9ea9d79846c1fba20a33MD51ORIGINALMariana Rosa Ampuero. Avaliação do papel... 2019.pdfMariana Rosa Ampuero. 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dc.title.pt_BR.fl_str_mv |
Avaliação do papel da via de sinalização de TREM-1 na leishmaniose cutânea localizada (LCL) humana |
title |
Avaliação do papel da via de sinalização de TREM-1 na leishmaniose cutânea localizada (LCL) humana |
spellingShingle |
Avaliação do papel da via de sinalização de TREM-1 na leishmaniose cutânea localizada (LCL) humana Ampuero, Mariana Rosa Leishmania braziliensis Leishmania cutânea localizada Neutrófilos Células mielóides Leishmania braziliensis Localized Cutaneous Leishmaniasis Human neutrophils Myeloid Cells |
title_short |
Avaliação do papel da via de sinalização de TREM-1 na leishmaniose cutânea localizada (LCL) humana |
title_full |
Avaliação do papel da via de sinalização de TREM-1 na leishmaniose cutânea localizada (LCL) humana |
title_fullStr |
Avaliação do papel da via de sinalização de TREM-1 na leishmaniose cutânea localizada (LCL) humana |
title_full_unstemmed |
Avaliação do papel da via de sinalização de TREM-1 na leishmaniose cutânea localizada (LCL) humana |
title_sort |
Avaliação do papel da via de sinalização de TREM-1 na leishmaniose cutânea localizada (LCL) humana |
author |
Ampuero, Mariana Rosa |
author_facet |
Ampuero, Mariana Rosa |
author_role |
author |
dc.contributor.member.none.fl_str_mv |
Prates, Deboraci Brito Carvalho, Lucas Pedreira de Tavares, Natália Machado |
dc.contributor.author.fl_str_mv |
Ampuero, Mariana Rosa |
dc.contributor.advisor1.fl_str_mv |
Tavares, Natalia Machado |
contributor_str_mv |
Tavares, Natalia Machado |
dc.subject.other.pt_BR.fl_str_mv |
Leishmania braziliensis Leishmania cutânea localizada Neutrófilos Células mielóides |
topic |
Leishmania braziliensis Leishmania cutânea localizada Neutrófilos Células mielóides Leishmania braziliensis Localized Cutaneous Leishmaniasis Human neutrophils Myeloid Cells |
dc.subject.en.pt_BR.fl_str_mv |
Leishmania braziliensis Localized Cutaneous Leishmaniasis Human neutrophils Myeloid Cells |
description |
Leishmaniasis remains one of the most neglected tropical diseases in the world. The immune response of the host against Leishmania plays a critical role in promoting parasite death and also promotes the severity of the disease. The Myeloid Cell Expression Receptor (TREM) has recently been identified as an immune response amplifier, which acts synergistically with Toll-like receptors (TLRs) in the production of pro-inflammatory mediators. TREM-1 is expressed strictly in myeloide lineage cells, mainly neutrophils. Its signaling form depends on the adaptive protein DAP12, which results in the activation of NFêB and the expression of reference genes, as well as in the degranulation, production of ROS and cytokines. OBJECTIVE: Based on this, the present study investigated the role of TREM-1 during L. braziliensis infection. MATERIAL AND METHODS: First, public transcriptome data of lesions from patients infected by L. braziliensis compared to not infected skin obtained from GEODataSets. After, the results were validated by real-time PCR with new samples. Finally, the mechanisms of activation of TREM-1 during human neutrophil infection in vitro were investigated. RESULTS: The transcriptome data analysis demonstrated an increase in TREM-1 expression, including all signaling molecules. These results were confirmed by RT-qPCR and immunohistochemistry in new samples. On the other hand, a negative correlation of messenger RNA of TREM-1, DAP12, TLR2 and TLR4 was observed on the circulating neutrophils of these patients. In addition, exposure to L. braziliensis increased the expression of TREM-1 on the surface of human neutrophils, leading to the degranulation of matrix metalloproteinase 9. Finally, TREM-1 and TLR2 are synergists in neutrophil degeneration but not in internalization of L brasiliensis. CONCLUSION: TREM-1 may be a potential target for modulation of inflammatory response in LCL, remaining the ability of neutrophil to kill Leishmania. |
publishDate |
2019 |
dc.date.accessioned.fl_str_mv |
2019-11-25T16:05:52Z |
dc.date.available.fl_str_mv |
2019-11-25T16:05:52Z |
dc.date.issued.fl_str_mv |
2019 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
AMPUERO, Mariana Rosa. Avaliação do papel da via de sinalização de TREM-1 na leishmaniose cutânea localizada (LCL) humana. 2019. 63 f. Dissertação (Mestrado em Patologia) – Universidade Federal da Bahia; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, 2019. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/37358 |
identifier_str_mv |
AMPUERO, Mariana Rosa. Avaliação do papel da via de sinalização de TREM-1 na leishmaniose cutânea localizada (LCL) humana. 2019. 63 f. Dissertação (Mestrado em Patologia) – Universidade Federal da Bahia; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, 2019. |
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https://www.arca.fiocruz.br/handle/icict/37358 |
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por |
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por |
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openAccess |
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Instituto Gonçalo Moniz |
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Instituto Gonçalo Moniz |
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Repositório Institucional da FIOCRUZ (ARCA) |
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