Dimorphism and dissemination of histoplasma capsulatum in the upper respiratory tract after intranasal infection of bats and mice with mycelial propagules
ABSTRACT: This article describes, for the first time, the role of the nasal mucosa (NM) as the initial site for the Histoplasma capsulatum mycelial-to-yeast transition. The results highlight that yeasts may arrive to the cervical lymph nodes (CLN) via phagocytes. Bats and mice were intranasally infe...
- Autores:
-
Sahaza Cardona, Jorge Humberto
Suárez Álvarez, Roberto O.
Berzunza Cruz, Miriam
Becker, Ingeborg
Curiel Quesada, Everardo
Pérez Torres, Armando
Reyes Montes, María del Rocío
Taylor, María Lucía
- Tipo de recurso:
- Article of investigation
- Fecha de publicación:
- 2019
- Institución:
- Universidad de Antioquia
- Repositorio:
- Repositorio UdeA
- Idioma:
- eng
- OAI Identifier:
- oai:bibliotecadigital.udea.edu.co:10495/38836
- Acceso en línea:
- https://hdl.handle.net/10495/38836
- Palabra clave:
- Adaptación Fisiológica
Adaptation, Physiological
Animales
Animals
Quirópteros - microbiología
Chiroptera - microbiology
Células Dendríticas - microbiología
Dendritic Cells - microbiology
Femenino
Female
Histoplasma - genética
Histoplasma - genetics
Histoplasma - fisiología
Histoplasma - physiology
Ganglios Linfáticos - microbiología
Lymph Nodes - microbiology
Ratones
Mice
Ratones Endogámicos C57BL
Mice, Inbred C57BL
Micelio - genética
Mycelium - genetics
Micelio - fisiología
Mycelium - physiology
Mucosa Nasal - microbiología
Nasal Mucosa - microbiology
Fagocitosis
Phagocytosis
Infecciones del Sistema Respiratorio - microbiología
Respiratory Tract Infections - microbiology
https://id.nlm.nih.gov/mesh/D000222
https://id.nlm.nih.gov/mesh/D000818
https://id.nlm.nih.gov/mesh/D002685
https://id.nlm.nih.gov/mesh/D003713
https://id.nlm.nih.gov/mesh/D005260
https://id.nlm.nih.gov/mesh/D006658
https://id.nlm.nih.gov/mesh/D008198
https://id.nlm.nih.gov/mesh/D051379
https://id.nlm.nih.gov/mesh/D008810
https://id.nlm.nih.gov/mesh/D025282
https://id.nlm.nih.gov/mesh/D009297
https://id.nlm.nih.gov/mesh/D010587
https://id.nlm.nih.gov/mesh/D012141
- Rights
- openAccess
- License
- https://creativecommons.org/licenses/by/4.0/
| id |
UDEA2_9a2c6cab411c1d388e090bbff46b6567 |
|---|---|
| oai_identifier_str |
oai:bibliotecadigital.udea.edu.co:10495/38836 |
| network_acronym_str |
UDEA2 |
| network_name_str |
Repositorio UdeA |
| repository_id_str |
|
| dc.title.spa.fl_str_mv |
Dimorphism and dissemination of histoplasma capsulatum in the upper respiratory tract after intranasal infection of bats and mice with mycelial propagules |
| title |
Dimorphism and dissemination of histoplasma capsulatum in the upper respiratory tract after intranasal infection of bats and mice with mycelial propagules |
| spellingShingle |
Dimorphism and dissemination of histoplasma capsulatum in the upper respiratory tract after intranasal infection of bats and mice with mycelial propagules Adaptación Fisiológica Adaptation, Physiological Animales Animals Quirópteros - microbiología Chiroptera - microbiology Células Dendríticas - microbiología Dendritic Cells - microbiology Femenino Female Histoplasma - genética Histoplasma - genetics Histoplasma - fisiología Histoplasma - physiology Ganglios Linfáticos - microbiología Lymph Nodes - microbiology Ratones Mice Ratones Endogámicos C57BL Mice, Inbred C57BL Micelio - genética Mycelium - genetics Micelio - fisiología Mycelium - physiology Mucosa Nasal - microbiología Nasal Mucosa - microbiology Fagocitosis Phagocytosis Infecciones del Sistema Respiratorio - microbiología Respiratory Tract Infections - microbiology https://id.nlm.nih.gov/mesh/D000222 https://id.nlm.nih.gov/mesh/D000818 https://id.nlm.nih.gov/mesh/D002685 https://id.nlm.nih.gov/mesh/D003713 https://id.nlm.nih.gov/mesh/D005260 https://id.nlm.nih.gov/mesh/D006658 https://id.nlm.nih.gov/mesh/D008198 https://id.nlm.nih.gov/mesh/D051379 https://id.nlm.nih.gov/mesh/D008810 https://id.nlm.nih.gov/mesh/D025282 https://id.nlm.nih.gov/mesh/D009297 https://id.nlm.nih.gov/mesh/D010587 https://id.nlm.nih.gov/mesh/D012141 |
| title_short |
Dimorphism and dissemination of histoplasma capsulatum in the upper respiratory tract after intranasal infection of bats and mice with mycelial propagules |
| title_full |
Dimorphism and dissemination of histoplasma capsulatum in the upper respiratory tract after intranasal infection of bats and mice with mycelial propagules |
| title_fullStr |
Dimorphism and dissemination of histoplasma capsulatum in the upper respiratory tract after intranasal infection of bats and mice with mycelial propagules |
| title_full_unstemmed |
Dimorphism and dissemination of histoplasma capsulatum in the upper respiratory tract after intranasal infection of bats and mice with mycelial propagules |
| title_sort |
Dimorphism and dissemination of histoplasma capsulatum in the upper respiratory tract after intranasal infection of bats and mice with mycelial propagules |
| dc.creator.fl_str_mv |
Sahaza Cardona, Jorge Humberto Suárez Álvarez, Roberto O. Berzunza Cruz, Miriam Becker, Ingeborg Curiel Quesada, Everardo Pérez Torres, Armando Reyes Montes, María del Rocío Taylor, María Lucía |
| dc.contributor.author.none.fl_str_mv |
Sahaza Cardona, Jorge Humberto Suárez Álvarez, Roberto O. Berzunza Cruz, Miriam Becker, Ingeborg Curiel Quesada, Everardo Pérez Torres, Armando Reyes Montes, María del Rocío Taylor, María Lucía |
| dc.contributor.researchgroup.spa.fl_str_mv |
Grupo de Investigación en Ciencia Sensorial |
| dc.subject.decs.none.fl_str_mv |
Adaptación Fisiológica Adaptation, Physiological Animales Animals Quirópteros - microbiología Chiroptera - microbiology Células Dendríticas - microbiología Dendritic Cells - microbiology Femenino Female Histoplasma - genética Histoplasma - genetics Histoplasma - fisiología Histoplasma - physiology Ganglios Linfáticos - microbiología Lymph Nodes - microbiology Ratones Mice Ratones Endogámicos C57BL Mice, Inbred C57BL Micelio - genética Mycelium - genetics Micelio - fisiología Mycelium - physiology Mucosa Nasal - microbiología Nasal Mucosa - microbiology Fagocitosis Phagocytosis Infecciones del Sistema Respiratorio - microbiología Respiratory Tract Infections - microbiology |
| topic |
Adaptación Fisiológica Adaptation, Physiological Animales Animals Quirópteros - microbiología Chiroptera - microbiology Células Dendríticas - microbiología Dendritic Cells - microbiology Femenino Female Histoplasma - genética Histoplasma - genetics Histoplasma - fisiología Histoplasma - physiology Ganglios Linfáticos - microbiología Lymph Nodes - microbiology Ratones Mice Ratones Endogámicos C57BL Mice, Inbred C57BL Micelio - genética Mycelium - genetics Micelio - fisiología Mycelium - physiology Mucosa Nasal - microbiología Nasal Mucosa - microbiology Fagocitosis Phagocytosis Infecciones del Sistema Respiratorio - microbiología Respiratory Tract Infections - microbiology https://id.nlm.nih.gov/mesh/D000222 https://id.nlm.nih.gov/mesh/D000818 https://id.nlm.nih.gov/mesh/D002685 https://id.nlm.nih.gov/mesh/D003713 https://id.nlm.nih.gov/mesh/D005260 https://id.nlm.nih.gov/mesh/D006658 https://id.nlm.nih.gov/mesh/D008198 https://id.nlm.nih.gov/mesh/D051379 https://id.nlm.nih.gov/mesh/D008810 https://id.nlm.nih.gov/mesh/D025282 https://id.nlm.nih.gov/mesh/D009297 https://id.nlm.nih.gov/mesh/D010587 https://id.nlm.nih.gov/mesh/D012141 |
| dc.subject.meshuri.none.fl_str_mv |
https://id.nlm.nih.gov/mesh/D000222 https://id.nlm.nih.gov/mesh/D000818 https://id.nlm.nih.gov/mesh/D002685 https://id.nlm.nih.gov/mesh/D003713 https://id.nlm.nih.gov/mesh/D005260 https://id.nlm.nih.gov/mesh/D006658 https://id.nlm.nih.gov/mesh/D008198 https://id.nlm.nih.gov/mesh/D051379 https://id.nlm.nih.gov/mesh/D008810 https://id.nlm.nih.gov/mesh/D025282 https://id.nlm.nih.gov/mesh/D009297 https://id.nlm.nih.gov/mesh/D010587 https://id.nlm.nih.gov/mesh/D012141 |
| description |
ABSTRACT: This article describes, for the first time, the role of the nasal mucosa (NM) as the initial site for the Histoplasma capsulatum mycelial-to-yeast transition. The results highlight that yeasts may arrive to the cervical lymph nodes (CLN) via phagocytes. Bats and mice were intranasally infected with H. capsulatum mycelial propagules and they were killed 10, 20, and 40 minutes and 1, 2, and 3 hours after infection. The NM and the CLN were monitored for fungal presence.Yeasts compatible with H. capsulatum were detected within the NM and the CLN dendritic cells (DCs) 2–3 hours postinfection, using immunohistochemistry. Histoplasma capsulatum was re-isolated by culturing at 28C from the CLN of both mammalian hosts 2–3 hours postinfection. Reverse transcription-polymerase chain reaction assays were designed to identify fungal dimorphism, using mycelial-specific (MS8) and yeast-specific (YPS3) gene expression. This strategy supported fast fungal dimorphism in vivo, which began in the NM 1 hour postinfection (a time point when MS8 and YPS3 genes were expressed) and it was completed at 3 hours (a time point when only the YPS3 transcripts were detected) in both bats and mice. The presence of intracellular yeasts in the nasal-associated lymphoid tissue (NALT), in the NM nonassociated with the NALT, and within the interdigitating DCs of the CLN suggests early fungal dissemination via the lymph vessels. |
| publishDate |
2019 |
| dc.date.issued.none.fl_str_mv |
2019 |
| dc.date.accessioned.none.fl_str_mv |
2024-03-27T21:00:13Z |
| dc.date.available.none.fl_str_mv |
2024-03-27T21:00:13Z |
| dc.type.spa.fl_str_mv |
Artículo de investigación |
| dc.type.coar.spa.fl_str_mv |
http://purl.org/coar/resource_type/c_2df8fbb1 |
| dc.type.redcol.spa.fl_str_mv |
https://purl.org/redcol/resource_type/ART |
| dc.type.coarversion.spa.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.driver.spa.fl_str_mv |
info:eu-repo/semantics/article |
| dc.type.version.spa.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| format |
http://purl.org/coar/resource_type/c_2df8fbb1 |
| status_str |
publishedVersion |
| dc.identifier.issn.none.fl_str_mv |
0002-9637 |
| dc.identifier.uri.none.fl_str_mv |
https://hdl.handle.net/10495/38836 |
| dc.identifier.doi.none.fl_str_mv |
10.4269/ajtmh.18-0788 |
| dc.identifier.eissn.none.fl_str_mv |
1476-1645 |
| identifier_str_mv |
0002-9637 10.4269/ajtmh.18-0788 1476-1645 |
| url |
https://hdl.handle.net/10495/38836 |
| dc.language.iso.spa.fl_str_mv |
eng |
| language |
eng |
| dc.relation.ispartofjournalabbrev.spa.fl_str_mv |
Am. J. Trop. Med. Hyg. |
| dc.relation.citationendpage.spa.fl_str_mv |
723 |
| dc.relation.citationissue.spa.fl_str_mv |
3 |
| dc.relation.citationstartpage.spa.fl_str_mv |
716 |
| dc.relation.citationvolume.spa.fl_str_mv |
101 |
| dc.relation.ispartofjournal.spa.fl_str_mv |
The American Journal of Tropical Medicine and Hygiene |
| dc.rights.uri.spa.fl_str_mv |
https://creativecommons.org/licenses/by/4.0/ |
| dc.rights.uri.*.fl_str_mv |
http://creativecommons.org/licenses/by/2.5/co/ |
| dc.rights.accessrights.spa.fl_str_mv |
info:eu-repo/semantics/openAccess |
| dc.rights.coar.spa.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
| rights_invalid_str_mv |
https://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/2.5/co/ http://purl.org/coar/access_right/c_abf2 |
| eu_rights_str_mv |
openAccess |
| dc.format.extent.spa.fl_str_mv |
8 páginas |
| dc.format.mimetype.spa.fl_str_mv |
application/pdf |
| dc.publisher.spa.fl_str_mv |
American Society of Tropical Medicine and Hygiene |
| dc.publisher.place.spa.fl_str_mv |
Northbrook, Estados Unidos |
| institution |
Universidad de Antioquia |
| bitstream.url.fl_str_mv |
https://bibliotecadigital.udea.edu.co/bitstreams/c81b32d6-c098-4132-b41b-50628645e304/download https://bibliotecadigital.udea.edu.co/bitstreams/6c989390-f110-479c-8f47-7ffb24a546d9/download https://bibliotecadigital.udea.edu.co/bitstreams/1aa67963-ce1b-4fa2-9b01-e817005fb990/download https://bibliotecadigital.udea.edu.co/bitstreams/05df8530-6010-4a01-ae01-f92ddd4d0705/download https://bibliotecadigital.udea.edu.co/bitstreams/bbb2d0bb-7777-4e17-b1be-ed66b0fe06a4/download |
| bitstream.checksum.fl_str_mv |
44da23534b26bebdc69b55b16035d235 1646d1f6b96dbbbc38035efc9239ac9c 8a4605be74aa9ea9d79846c1fba20a33 9dcfc346fae48920c9d5ee0afdffaf57 daf20ed935039c12c29218c43b0aa183 |
| bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 MD5 |
| repository.name.fl_str_mv |
Repositorio Institucional de la Universidad de Antioquia |
| repository.mail.fl_str_mv |
aplicacionbibliotecadigitalbiblioteca@udea.edu.co |
| _version_ |
1851052513738883072 |
| spelling |
Sahaza Cardona, Jorge HumbertoSuárez Álvarez, Roberto O.Berzunza Cruz, MiriamBecker, IngeborgCuriel Quesada, EverardoPérez Torres, ArmandoReyes Montes, María del RocíoTaylor, María LucíaGrupo de Investigación en Ciencia Sensorial2024-03-27T21:00:13Z2024-03-27T21:00:13Z20190002-9637https://hdl.handle.net/10495/3883610.4269/ajtmh.18-07881476-1645ABSTRACT: This article describes, for the first time, the role of the nasal mucosa (NM) as the initial site for the Histoplasma capsulatum mycelial-to-yeast transition. The results highlight that yeasts may arrive to the cervical lymph nodes (CLN) via phagocytes. Bats and mice were intranasally infected with H. capsulatum mycelial propagules and they were killed 10, 20, and 40 minutes and 1, 2, and 3 hours after infection. The NM and the CLN were monitored for fungal presence.Yeasts compatible with H. capsulatum were detected within the NM and the CLN dendritic cells (DCs) 2–3 hours postinfection, using immunohistochemistry. Histoplasma capsulatum was re-isolated by culturing at 28C from the CLN of both mammalian hosts 2–3 hours postinfection. Reverse transcription-polymerase chain reaction assays were designed to identify fungal dimorphism, using mycelial-specific (MS8) and yeast-specific (YPS3) gene expression. This strategy supported fast fungal dimorphism in vivo, which began in the NM 1 hour postinfection (a time point when MS8 and YPS3 genes were expressed) and it was completed at 3 hours (a time point when only the YPS3 transcripts were detected) in both bats and mice. The presence of intracellular yeasts in the nasal-associated lymphoid tissue (NALT), in the NM nonassociated with the NALT, and within the interdigitating DCs of the CLN suggests early fungal dissemination via the lymph vessels.Consejo Nacional de Humanidades, Ciencias y TecnologíasCOL01060398 páginasapplication/pdfengAmerican Society of Tropical Medicine and HygieneNorthbrook, Estados Unidoshttps://creativecommons.org/licenses/by/4.0/http://creativecommons.org/licenses/by/2.5/co/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Dimorphism and dissemination of histoplasma capsulatum in the upper respiratory tract after intranasal infection of bats and mice with mycelial propagulesArtículo de investigaciónhttp://purl.org/coar/resource_type/c_2df8fbb1https://purl.org/redcol/resource_type/ARThttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionAdaptación FisiológicaAdaptation, PhysiologicalAnimalesAnimalsQuirópteros - microbiologíaChiroptera - microbiologyCélulas Dendríticas - microbiologíaDendritic Cells - microbiologyFemeninoFemaleHistoplasma - genéticaHistoplasma - geneticsHistoplasma - fisiologíaHistoplasma - physiologyGanglios Linfáticos - microbiologíaLymph Nodes - microbiologyRatonesMiceRatones Endogámicos C57BLMice, Inbred C57BLMicelio - genéticaMycelium - geneticsMicelio - fisiologíaMycelium - physiologyMucosa Nasal - microbiologíaNasal Mucosa - microbiologyFagocitosisPhagocytosisInfecciones del Sistema Respiratorio - microbiologíaRespiratory Tract Infections - microbiologyhttps://id.nlm.nih.gov/mesh/D000222https://id.nlm.nih.gov/mesh/D000818https://id.nlm.nih.gov/mesh/D002685https://id.nlm.nih.gov/mesh/D003713https://id.nlm.nih.gov/mesh/D005260https://id.nlm.nih.gov/mesh/D006658https://id.nlm.nih.gov/mesh/D008198https://id.nlm.nih.gov/mesh/D051379https://id.nlm.nih.gov/mesh/D008810https://id.nlm.nih.gov/mesh/D025282https://id.nlm.nih.gov/mesh/D009297https://id.nlm.nih.gov/mesh/D010587https://id.nlm.nih.gov/mesh/D012141Am. J. Trop. Med. Hyg.7233716101The American Journal of Tropical Medicine and Hygiene182501 and 166052RoR:059ex5q34PublicationORIGINALSahazaJorge_2019_Dimorphism_Dissemination_Histoplasma_Capsulatum.pdfSahazaJorge_2019_Dimorphism_Dissemination_Histoplasma_Capsulatum.pdfArtículo de investigaciónapplication/pdf618460https://bibliotecadigital.udea.edu.co/bitstreams/c81b32d6-c098-4132-b41b-50628645e304/download44da23534b26bebdc69b55b16035d235MD51trueAnonymousREADCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8927https://bibliotecadigital.udea.edu.co/bitstreams/6c989390-f110-479c-8f47-7ffb24a546d9/download1646d1f6b96dbbbc38035efc9239ac9cMD52falseAnonymousREADLICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://bibliotecadigital.udea.edu.co/bitstreams/1aa67963-ce1b-4fa2-9b01-e817005fb990/download8a4605be74aa9ea9d79846c1fba20a33MD53falseAnonymousREADTEXTSahazaJorge_2019_Dimorphism_Dissemination_Histoplasma_Capsulatum.pdf.txtSahazaJorge_2019_Dimorphism_Dissemination_Histoplasma_Capsulatum.pdf.txtExtracted texttext/plain44498https://bibliotecadigital.udea.edu.co/bitstreams/05df8530-6010-4a01-ae01-f92ddd4d0705/download9dcfc346fae48920c9d5ee0afdffaf57MD54falseAnonymousREADTHUMBNAILSahazaJorge_2019_Dimorphism_Dissemination_Histoplasma_Capsulatum.pdf.jpgSahazaJorge_2019_Dimorphism_Dissemination_Histoplasma_Capsulatum.pdf.jpgGenerated Thumbnailimage/jpeg17637https://bibliotecadigital.udea.edu.co/bitstreams/bbb2d0bb-7777-4e17-b1be-ed66b0fe06a4/downloaddaf20ed935039c12c29218c43b0aa183MD55falseAnonymousREAD10495/38836oai:bibliotecadigital.udea.edu.co:10495/388362025-03-26 23:36:22.523https://creativecommons.org/licenses/by/4.0/open.accesshttps://bibliotecadigital.udea.edu.coRepositorio Institucional de la Universidad de Antioquiaaplicacionbibliotecadigitalbiblioteca@udea.edu.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 |
