Differences in Intracellular Fate of Two Spotted Fever Group Rickettsia in Macrophage-Like Cells
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/108591 https://doi.org/10.3389/fcimb.2016.00080 |
Resumo: | Spotted fever group (SFG) rickettsiae are recognized as important agents of human tick-borne diseases worldwide, such as Mediterranean spotted fever (Rickettsia conorii) and Rocky Mountain spotted fever (Rickettsia rickettsii). Recent studies in several animal models have provided evidence of non-endothelial parasitism by pathogenic SFG Rickettsia species, suggesting that the interaction of rickettsiae with cells other than the endothelium may play an important role in pathogenesis of rickettsial diseases. These studies raise the hypothesis that the role of macrophages in rickettsial pathogenesis may have been underappreciated. Herein, we evaluated the ability of two SFG rickettsial species, R. conorii (a recognized human pathogen) and Rickettsia montanensis (a non-virulent member of SFG) to proliferate in THP-1 macrophage-like cells, or within non-phagocytic cell lines. Our results demonstrate that R. conorii was able to survive and proliferate in both phagocytic and epithelial cells in vitro. In contrast, R. montanensis was able to grow in non-phagocytic cells, but was drastically compromised in the ability to proliferate within both undifferentiated and PMA-differentiated THP-1 cells. Interestingly, association assays revealed that R. montanensis was defective in binding to THP-1-derived macrophages; however, the invasion of the bacteria that are able to adhere did not appear to be affected. We have also demonstrated that R. montanensis which entered into THP-1-derived macrophages were rapidly destroyed and partially co-localized with LAMP-2 and cathepsin D, two markers of lysosomal compartments. In contrast, R. conorii was present as intact bacteria and free in the cytoplasm in both cell types. These findings suggest that a phenotypic difference between a non-pathogenic and a pathogenic SFG member lies in their respective ability to proliferate in macrophage-like cells, and may provide an explanation as to why certain SFG rickettsial species are not associated with disease in mammals. |
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Differences in Intracellular Fate of Two Spotted Fever Group Rickettsia in Macrophage-Like Cellsrickettsiaespottedfevergroup RickettsiamacrophagespathogenicityintracellularfateR.conoriiR.montanensisAnimalsCathepsin DCell LineChlorocebus aethiopsCytoplasmEpithelial CellsHost-Parasite InteractionsHumansIn Vitro TechniquesLysosomal-Associated Membrane Protein 2MacrophagesPhagocytesRickettsiaRocky Mountain Spotted FeverVero CellsSpotted fever group (SFG) rickettsiae are recognized as important agents of human tick-borne diseases worldwide, such as Mediterranean spotted fever (Rickettsia conorii) and Rocky Mountain spotted fever (Rickettsia rickettsii). Recent studies in several animal models have provided evidence of non-endothelial parasitism by pathogenic SFG Rickettsia species, suggesting that the interaction of rickettsiae with cells other than the endothelium may play an important role in pathogenesis of rickettsial diseases. These studies raise the hypothesis that the role of macrophages in rickettsial pathogenesis may have been underappreciated. Herein, we evaluated the ability of two SFG rickettsial species, R. conorii (a recognized human pathogen) and Rickettsia montanensis (a non-virulent member of SFG) to proliferate in THP-1 macrophage-like cells, or within non-phagocytic cell lines. Our results demonstrate that R. conorii was able to survive and proliferate in both phagocytic and epithelial cells in vitro. In contrast, R. montanensis was able to grow in non-phagocytic cells, but was drastically compromised in the ability to proliferate within both undifferentiated and PMA-differentiated THP-1 cells. Interestingly, association assays revealed that R. montanensis was defective in binding to THP-1-derived macrophages; however, the invasion of the bacteria that are able to adhere did not appear to be affected. We have also demonstrated that R. montanensis which entered into THP-1-derived macrophages were rapidly destroyed and partially co-localized with LAMP-2 and cathepsin D, two markers of lysosomal compartments. In contrast, R. conorii was present as intact bacteria and free in the cytoplasm in both cell types. These findings suggest that a phenotypic difference between a non-pathogenic and a pathogenic SFG member lies in their respective ability to proliferate in macrophage-like cells, and may provide an explanation as to why certain SFG rickettsial species are not associated with disease in mammals.Frontiers Media S.A.2016info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/108591http://hdl.handle.net/10316/108591https://doi.org/10.3389/fcimb.2016.00080eng2235-2988Curto, PedroSimões, IsauraRiley, Sean P.Martinez, Juan J.info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-09-04T11:40:23Zoai:estudogeral.uc.pt:10316/108591Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:24:53.101964Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Differences in Intracellular Fate of Two Spotted Fever Group Rickettsia in Macrophage-Like Cells |
title |
Differences in Intracellular Fate of Two Spotted Fever Group Rickettsia in Macrophage-Like Cells |
spellingShingle |
Differences in Intracellular Fate of Two Spotted Fever Group Rickettsia in Macrophage-Like Cells Curto, Pedro rickettsiae spottedfevergroup Rickettsia macrophages pathogenicity intracellularfate R.conorii R.montanensis Animals Cathepsin D Cell Line Chlorocebus aethiops Cytoplasm Epithelial Cells Host-Parasite Interactions Humans In Vitro Techniques Lysosomal-Associated Membrane Protein 2 Macrophages Phagocytes Rickettsia Rocky Mountain Spotted Fever Vero Cells |
title_short |
Differences in Intracellular Fate of Two Spotted Fever Group Rickettsia in Macrophage-Like Cells |
title_full |
Differences in Intracellular Fate of Two Spotted Fever Group Rickettsia in Macrophage-Like Cells |
title_fullStr |
Differences in Intracellular Fate of Two Spotted Fever Group Rickettsia in Macrophage-Like Cells |
title_full_unstemmed |
Differences in Intracellular Fate of Two Spotted Fever Group Rickettsia in Macrophage-Like Cells |
title_sort |
Differences in Intracellular Fate of Two Spotted Fever Group Rickettsia in Macrophage-Like Cells |
author |
Curto, Pedro |
author_facet |
Curto, Pedro Simões, Isaura Riley, Sean P. Martinez, Juan J. |
author_role |
author |
author2 |
Simões, Isaura Riley, Sean P. Martinez, Juan J. |
author2_role |
author author author |
dc.contributor.author.fl_str_mv |
Curto, Pedro Simões, Isaura Riley, Sean P. Martinez, Juan J. |
dc.subject.por.fl_str_mv |
rickettsiae spottedfevergroup Rickettsia macrophages pathogenicity intracellularfate R.conorii R.montanensis Animals Cathepsin D Cell Line Chlorocebus aethiops Cytoplasm Epithelial Cells Host-Parasite Interactions Humans In Vitro Techniques Lysosomal-Associated Membrane Protein 2 Macrophages Phagocytes Rickettsia Rocky Mountain Spotted Fever Vero Cells |
topic |
rickettsiae spottedfevergroup Rickettsia macrophages pathogenicity intracellularfate R.conorii R.montanensis Animals Cathepsin D Cell Line Chlorocebus aethiops Cytoplasm Epithelial Cells Host-Parasite Interactions Humans In Vitro Techniques Lysosomal-Associated Membrane Protein 2 Macrophages Phagocytes Rickettsia Rocky Mountain Spotted Fever Vero Cells |
description |
Spotted fever group (SFG) rickettsiae are recognized as important agents of human tick-borne diseases worldwide, such as Mediterranean spotted fever (Rickettsia conorii) and Rocky Mountain spotted fever (Rickettsia rickettsii). Recent studies in several animal models have provided evidence of non-endothelial parasitism by pathogenic SFG Rickettsia species, suggesting that the interaction of rickettsiae with cells other than the endothelium may play an important role in pathogenesis of rickettsial diseases. These studies raise the hypothesis that the role of macrophages in rickettsial pathogenesis may have been underappreciated. Herein, we evaluated the ability of two SFG rickettsial species, R. conorii (a recognized human pathogen) and Rickettsia montanensis (a non-virulent member of SFG) to proliferate in THP-1 macrophage-like cells, or within non-phagocytic cell lines. Our results demonstrate that R. conorii was able to survive and proliferate in both phagocytic and epithelial cells in vitro. In contrast, R. montanensis was able to grow in non-phagocytic cells, but was drastically compromised in the ability to proliferate within both undifferentiated and PMA-differentiated THP-1 cells. Interestingly, association assays revealed that R. montanensis was defective in binding to THP-1-derived macrophages; however, the invasion of the bacteria that are able to adhere did not appear to be affected. We have also demonstrated that R. montanensis which entered into THP-1-derived macrophages were rapidly destroyed and partially co-localized with LAMP-2 and cathepsin D, two markers of lysosomal compartments. In contrast, R. conorii was present as intact bacteria and free in the cytoplasm in both cell types. These findings suggest that a phenotypic difference between a non-pathogenic and a pathogenic SFG member lies in their respective ability to proliferate in macrophage-like cells, and may provide an explanation as to why certain SFG rickettsial species are not associated with disease in mammals. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/108591 http://hdl.handle.net/10316/108591 https://doi.org/10.3389/fcimb.2016.00080 |
url |
http://hdl.handle.net/10316/108591 https://doi.org/10.3389/fcimb.2016.00080 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2235-2988 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Frontiers Media S.A. |
publisher.none.fl_str_mv |
Frontiers Media S.A. |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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