HIV-1-exposed seronegative individuals show alteration in TLR expression and pro-inflammatory cytokine production ex vivo: An innate immune quiescence status?
Pattern recognition receptors (PRRs) are involved in direct recognition of viruses, promoting cellular activation and the production of pro-inflammatory cytokines. However, despite the reduced systemic immune activation described in HIV-1-exposed seronegatives (HESNs), few studies have focused on de...
- Autores:
-
Hernández López, Juan Carlos
St. Laurent III, Georges
Urucqui Inchima, Silvio
- Tipo de recurso:
- Article of journal
- Fecha de publicación:
- 2016
- Institución:
- Universidad Cooperativa de Colombia
- Repositorio:
- Repositorio UCC
- Idioma:
- OAI Identifier:
- oai:repository.ucc.edu.co:20.500.12494/1185
- Acceso en línea:
- https://hdl.handle.net/20.500.12494/1185
- Palabra clave:
- HIV-1
Inflammation
- Rights
- openAccess
- License
- Licencia CC
id |
COOPER2_a6fe1903b88f2ea2309a813ca7eea3fd |
---|---|
oai_identifier_str |
oai:repository.ucc.edu.co:20.500.12494/1185 |
network_acronym_str |
COOPER2 |
network_name_str |
Repositorio UCC |
repository_id_str |
|
dc.title.spa.fl_str_mv |
HIV-1-exposed seronegative individuals show alteration in TLR expression and pro-inflammatory cytokine production ex vivo: An innate immune quiescence status? |
title |
HIV-1-exposed seronegative individuals show alteration in TLR expression and pro-inflammatory cytokine production ex vivo: An innate immune quiescence status? |
spellingShingle |
HIV-1-exposed seronegative individuals show alteration in TLR expression and pro-inflammatory cytokine production ex vivo: An innate immune quiescence status? HIV-1 Inflammation |
title_short |
HIV-1-exposed seronegative individuals show alteration in TLR expression and pro-inflammatory cytokine production ex vivo: An innate immune quiescence status? |
title_full |
HIV-1-exposed seronegative individuals show alteration in TLR expression and pro-inflammatory cytokine production ex vivo: An innate immune quiescence status? |
title_fullStr |
HIV-1-exposed seronegative individuals show alteration in TLR expression and pro-inflammatory cytokine production ex vivo: An innate immune quiescence status? |
title_full_unstemmed |
HIV-1-exposed seronegative individuals show alteration in TLR expression and pro-inflammatory cytokine production ex vivo: An innate immune quiescence status? |
title_sort |
HIV-1-exposed seronegative individuals show alteration in TLR expression and pro-inflammatory cytokine production ex vivo: An innate immune quiescence status? |
dc.creator.fl_str_mv |
Hernández López, Juan Carlos St. Laurent III, Georges Urucqui Inchima, Silvio |
dc.contributor.author.none.fl_str_mv |
Hernández López, Juan Carlos St. Laurent III, Georges Urucqui Inchima, Silvio |
dc.subject.spa.fl_str_mv |
HIV-1 Inflammation |
topic |
HIV-1 Inflammation |
description |
Pattern recognition receptors (PRRs) are involved in direct recognition of viruses, promoting cellular activation and the production of pro-inflammatory cytokines. However, despite the reduced systemic immune activation described in HIV-1-exposed seronegatives (HESNs), few studies have focused on determining the relationship between PRR expression and cytokine production. We have aimed here to evaluate the expression level of PRRs and cytokines in HESNs, HIV-1 patients and healthy donors. Basal PRR expression levels in PBMCs, dendritic cells (DCs) and monocytes, and plasma cytokine levels as well as the PRR ligand-induced cytokine productions were determined by flow cytometry, qPCR and ELISA. Higher TLR2/4 expression in DCs and monocytes from HESNs was observed. Nevertheless, TLR4/8, NOD2 and RIG-I mRNA levels were lower in PBMCs from HESNs than HIV-1-infected patients. Comparable IL-1b, IL-18 and TNF-a mRNA levels were observed among the groups examined; however, at the protein level, production of IL-1b, IL-6 and IL-10 was significantly lower in plasma from HESNs than from HIV-1-infected patients. Our results suggest that exposure to HIV-1 without infection could be associated with reduced basal proinflammatory responses. Further studies are required to define the cell subsets responsible for these differences and the role of PRRs on protection against HIV-1 infection. |
publishDate |
2016 |
dc.date.issued.none.fl_str_mv |
2016-02 |
dc.date.accessioned.none.fl_str_mv |
2017-08-18T23:22:11Z |
dc.date.available.none.fl_str_mv |
2017-08-18T23:22:11Z |
dc.type.none.fl_str_mv |
Artículo |
dc.type.coar.fl_str_mv |
http://purl.org/coar/resource_type/c_2df8fbb1 |
dc.type.coar.none.fl_str_mv |
http://purl.org/coar/resource_type/c_6501 |
dc.type.coarversion.none.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
dc.type.driver.none.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.version.none.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
http://purl.org/coar/resource_type/c_6501 |
status_str |
publishedVersion |
dc.identifier.uri.none.fl_str_mv |
https://hdl.handle.net/20.500.12494/1185 |
dc.identifier.bibliographicCitation.spa.fl_str_mv |
Hernández, J. C., St. Laurent 3rd, Urcuqui Inchima, S. (2016). HIV-1-exposed seronegative individuals show alteration in TLR expression and pro-inflammatory cytokine production ex vivo: An innate immune quiescence status? Immunologic Research, 64(1), 280-290. doi: 10.1007/s12026-015-8748-8. |
url |
https://hdl.handle.net/20.500.12494/1185 |
identifier_str_mv |
Hernández, J. C., St. Laurent 3rd, Urcuqui Inchima, S. (2016). HIV-1-exposed seronegative individuals show alteration in TLR expression and pro-inflammatory cytokine production ex vivo: An innate immune quiescence status? Immunologic Research, 64(1), 280-290. doi: 10.1007/s12026-015-8748-8. |
dc.relation.isversionof.spa.fl_str_mv |
https://link.springer.com/article/10.1007%2Fs12026-015-8748-8 |
dc.rights.cc.none.fl_str_mv |
Licencia CC |
dc.rights.accessrights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
dc.rights.coar.none.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
rights_invalid_str_mv |
Licencia CC http://purl.org/coar/access_right/c_abf2 |
eu_rights_str_mv |
openAccess |
dc.publisher.spa.fl_str_mv |
Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Programa de Medicina, Medellín y Envigado, Colombia, 00000 |
dc.publisher.program.spa.fl_str_mv |
Medicina |
dc.publisher.place.spa.fl_str_mv |
Medellín |
institution |
Universidad Cooperativa de Colombia |
bitstream.url.fl_str_mv |
https://repository.ucc.edu.co/bitstreams/6601abf1-16aa-40ed-ac50-459a09c3f908/download https://repository.ucc.edu.co/bitstreams/88aad2a3-cdc7-481c-ba5a-a5b8d3d1a283/download https://repository.ucc.edu.co/bitstreams/4c53f489-91d2-4c12-8f09-d7d76c7b992c/download https://repository.ucc.edu.co/bitstreams/cfb11d8e-db3f-42ce-9de6-7a5f734d3bf7/download |
bitstream.checksum.fl_str_mv |
cb8f4d9b72d863ad6737f22af442cc82 2988b493af59b56566ff4101c723797b 0cdf8b8bdb596567273e55eb7dba4147 caa9b23cc3f4de64dcd7d66fdab7146a |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositorio Institucional Universidad Cooperativa de Colombia |
repository.mail.fl_str_mv |
bdigital@metabiblioteca.com |
_version_ |
1814247092004061184 |
spelling |
Hernández López, Juan CarlosSt. Laurent III, GeorgesUrucqui Inchima, Silvio2017-08-18T23:22:11Z2017-08-18T23:22:11Z2016-02https://hdl.handle.net/20.500.12494/1185Hernández, J. C., St. Laurent 3rd, Urcuqui Inchima, S. (2016). HIV-1-exposed seronegative individuals show alteration in TLR expression and pro-inflammatory cytokine production ex vivo: An innate immune quiescence status? Immunologic Research, 64(1), 280-290. doi: 10.1007/s12026-015-8748-8.Pattern recognition receptors (PRRs) are involved in direct recognition of viruses, promoting cellular activation and the production of pro-inflammatory cytokines. However, despite the reduced systemic immune activation described in HIV-1-exposed seronegatives (HESNs), few studies have focused on determining the relationship between PRR expression and cytokine production. We have aimed here to evaluate the expression level of PRRs and cytokines in HESNs, HIV-1 patients and healthy donors. Basal PRR expression levels in PBMCs, dendritic cells (DCs) and monocytes, and plasma cytokine levels as well as the PRR ligand-induced cytokine productions were determined by flow cytometry, qPCR and ELISA. Higher TLR2/4 expression in DCs and monocytes from HESNs was observed. Nevertheless, TLR4/8, NOD2 and RIG-I mRNA levels were lower in PBMCs from HESNs than HIV-1-infected patients. Comparable IL-1b, IL-18 and TNF-a mRNA levels were observed among the groups examined; however, at the protein level, production of IL-1b, IL-6 and IL-10 was significantly lower in plasma from HESNs than from HIV-1-infected patients. Our results suggest that exposure to HIV-1 without infection could be associated with reduced basal proinflammatory responses. Further studies are required to define the cell subsets responsible for these differences and the role of PRRs on protection against HIV-1 infection.juanc.hernandezl@campusucc.edu.coUniversidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Programa de Medicina, Medellín y Envigado, Colombia, 00000MedicinaMedellínhttps://link.springer.com/article/10.1007%2Fs12026-015-8748-8HIV-1InflammationHIV-1-exposed seronegative individuals show alteration in TLR expression and pro-inflammatory cytokine production ex vivo: An innate immune quiescence status?Artículohttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1http://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionLicencia CCinfo:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2PublicationLICENSElicense.txtlicense.txttext/plain; charset=utf-84553https://repository.ucc.edu.co/bitstreams/6601abf1-16aa-40ed-ac50-459a09c3f908/downloadcb8f4d9b72d863ad6737f22af442cc82MD52TEXTpost-print.pdf.txtpost-print.pdf.txtExtracted texttext/plain44442https://repository.ucc.edu.co/bitstreams/88aad2a3-cdc7-481c-ba5a-a5b8d3d1a283/download2988b493af59b56566ff4101c723797bMD53THUMBNAILpost-print.pdf.jpgpost-print.pdf.jpgIM Thumbnailimage/jpeg4072https://repository.ucc.edu.co/bitstreams/4c53f489-91d2-4c12-8f09-d7d76c7b992c/download0cdf8b8bdb596567273e55eb7dba4147MD54ORIGINALpost-print.pdfpost-print.pdfapplication/pdf549893https://repository.ucc.edu.co/bitstreams/cfb11d8e-db3f-42ce-9de6-7a5f734d3bf7/downloadcaa9b23cc3f4de64dcd7d66fdab7146aMD5120.500.12494/1185oai:repository.ucc.edu.co:20.500.12494/11852024-08-10 22:44:17.335open.accesshttps://repository.ucc.edu.coRepositorio Institucional Universidad Cooperativa de Colombiabdigital@metabiblioteca.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 |