Vitamin D-induced LL-37 modulates innate immune responses of human primary macrophages during DENV-2 infection

ABSTRACT: Epidemics of dengue, an acute and potentially severe disease caused by mosquito-borne dengue virus (DENV), pose a major challenge to clinicians and health care services across the sub(tropics). Severe disease onset is associated with a dysregulated inflammatory response to the virus, and t...

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Autores:
Castillo Ramírez, Jorge Andrés
Giraldo Giraldo, Diana Marcela
Rodenhuis Zybert, Izabela Agata
Smit, Jolanda
Urcuqui Inchima, Silvio
Tipo de recurso:
Article of investigation
Fecha de publicación:
2022
Institución:
Universidad de Antioquia
Repositorio:
Repositorio UdeA
Idioma:
eng
OAI Identifier:
oai:bibliotecadigital.udea.edu.co:10495/29734
Acceso en línea:
https://hdl.handle.net/10495/29734
Palabra clave:
Virus del Dengue
Dengue Virus
Macrófagos
Macrophages
Inmunidad Innata
Immunity, Innate
Vitamina D
Vitamin D
LL-37
Rights
openAccess
License
http://creativecommons.org/licenses/by-nc-sa/2.5/co/
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network_acronym_str UDEA2
network_name_str Repositorio UdeA
repository_id_str
dc.title.spa.fl_str_mv Vitamin D-induced LL-37 modulates innate immune responses of human primary macrophages during DENV-2 infection
title Vitamin D-induced LL-37 modulates innate immune responses of human primary macrophages during DENV-2 infection
spellingShingle Vitamin D-induced LL-37 modulates innate immune responses of human primary macrophages during DENV-2 infection
Virus del Dengue
Dengue Virus
Macrófagos
Macrophages
Inmunidad Innata
Immunity, Innate
Vitamina D
Vitamin D
LL-37
title_short Vitamin D-induced LL-37 modulates innate immune responses of human primary macrophages during DENV-2 infection
title_full Vitamin D-induced LL-37 modulates innate immune responses of human primary macrophages during DENV-2 infection
title_fullStr Vitamin D-induced LL-37 modulates innate immune responses of human primary macrophages during DENV-2 infection
title_full_unstemmed Vitamin D-induced LL-37 modulates innate immune responses of human primary macrophages during DENV-2 infection
title_sort Vitamin D-induced LL-37 modulates innate immune responses of human primary macrophages during DENV-2 infection
dc.creator.fl_str_mv Castillo Ramírez, Jorge Andrés
Giraldo Giraldo, Diana Marcela
Rodenhuis Zybert, Izabela Agata
Smit, Jolanda
Urcuqui Inchima, Silvio
dc.contributor.author.none.fl_str_mv Castillo Ramírez, Jorge Andrés
Giraldo Giraldo, Diana Marcela
Rodenhuis Zybert, Izabela Agata
Smit, Jolanda
Urcuqui Inchima, Silvio
dc.contributor.researchgroup.spa.fl_str_mv Inmunovirología
dc.subject.decs.none.fl_str_mv Virus del Dengue
Dengue Virus
Macrófagos
Macrophages
Inmunidad Innata
Immunity, Innate
Vitamina D
Vitamin D
topic Virus del Dengue
Dengue Virus
Macrófagos
Macrophages
Inmunidad Innata
Immunity, Innate
Vitamina D
Vitamin D
LL-37
dc.subject.proposal.spa.fl_str_mv LL-37
description ABSTRACT: Epidemics of dengue, an acute and potentially severe disease caused by mosquito-borne dengue virus (DENV), pose a major challenge to clinicians and health care services across the sub(tropics). Severe disease onset is associated with a dysregulated inflammatory response to the virus, and there are currently no drugs to alleviate disease symptoms. LL-37 is a potent antimicrobial peptide with a wide range of immunoregulatory properties. In this study, we assessed the effect of LL-37 on DENV-2-induced responses in human monocyte-derived macrophages (MDMs). We show that simultaneous exposure of exogenous LL-37 and DENV-2 resulted in reduced replication of the virus in MDMs, while the addition of LL-37 postexposure to DENV-2 did not. Interestingly, the latter condition reduced the production of IL-6 and increased the expression of genes involved in virus sensing and antiviral response. Finally, we demonstrate that low endogenous levels and limited production of LL-37 in MDMs in response to DENV-2 infection can be increased by differentiating MDMs in the presence of Vitamin D (VitD3). Taken together, this study demonstrates that in addition to its antimicrobial properties, LL-37 has immunomodulatory properties in the curse of DENV infection and its production can be increased by VitD3.
publishDate 2022
dc.date.accessioned.none.fl_str_mv 2022-07-14T15:44:10Z
dc.date.available.none.fl_str_mv 2022-07-14T15:44:10Z
dc.date.issued.none.fl_str_mv 2022
dc.type.spa.fl_str_mv Artículo de investigación
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dc.identifier.citation.spa.fl_str_mv Castillo JA, Giraldo DM, Smit JM, Rodenhuis-Zybert IA, Urcuqui-Inchima S. Vitamin D-induced LL-37 modulates innate immune responses of human primary macrophages during DENV-2 infection. Pathog Dis. 2022 May 23;80(1):ftac014. doi: 10.1093/femspd/ftac014.
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/10495/29734
dc.identifier.doi.none.fl_str_mv 10.1093/femspd/ftac014
dc.identifier.eissn.none.fl_str_mv 2049-632X
identifier_str_mv Castillo JA, Giraldo DM, Smit JM, Rodenhuis-Zybert IA, Urcuqui-Inchima S. Vitamin D-induced LL-37 modulates innate immune responses of human primary macrophages during DENV-2 infection. Pathog Dis. 2022 May 23;80(1):ftac014. doi: 10.1093/femspd/ftac014.
10.1093/femspd/ftac014
2049-632X
url https://hdl.handle.net/10495/29734
dc.language.iso.spa.fl_str_mv eng
language eng
dc.relation.ispartofjournalabbrev.spa.fl_str_mv Pathog. Dis.
dc.relation.citationendpage.spa.fl_str_mv 11
dc.relation.citationissue.spa.fl_str_mv 1
dc.relation.citationstartpage.spa.fl_str_mv 1
dc.relation.citationvolume.spa.fl_str_mv 80
dc.relation.ispartofjournal.spa.fl_str_mv Pathogens and Disease
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dc.format.extent.spa.fl_str_mv 11
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dc.publisher.spa.fl_str_mv Oxford University Press
dc.publisher.place.spa.fl_str_mv Oxford, Estados Unidos
institution Universidad de Antioquia
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spelling Castillo Ramírez, Jorge AndrésGiraldo Giraldo, Diana MarcelaRodenhuis Zybert, Izabela AgataSmit, JolandaUrcuqui Inchima, SilvioInmunovirología2022-07-14T15:44:10Z2022-07-14T15:44:10Z2022Castillo JA, Giraldo DM, Smit JM, Rodenhuis-Zybert IA, Urcuqui-Inchima S. Vitamin D-induced LL-37 modulates innate immune responses of human primary macrophages during DENV-2 infection. Pathog Dis. 2022 May 23;80(1):ftac014. doi: 10.1093/femspd/ftac014.https://hdl.handle.net/10495/2973410.1093/femspd/ftac0142049-632XABSTRACT: Epidemics of dengue, an acute and potentially severe disease caused by mosquito-borne dengue virus (DENV), pose a major challenge to clinicians and health care services across the sub(tropics). Severe disease onset is associated with a dysregulated inflammatory response to the virus, and there are currently no drugs to alleviate disease symptoms. LL-37 is a potent antimicrobial peptide with a wide range of immunoregulatory properties. In this study, we assessed the effect of LL-37 on DENV-2-induced responses in human monocyte-derived macrophages (MDMs). We show that simultaneous exposure of exogenous LL-37 and DENV-2 resulted in reduced replication of the virus in MDMs, while the addition of LL-37 postexposure to DENV-2 did not. Interestingly, the latter condition reduced the production of IL-6 and increased the expression of genes involved in virus sensing and antiviral response. Finally, we demonstrate that low endogenous levels and limited production of LL-37 in MDMs in response to DENV-2 infection can be increased by differentiating MDMs in the presence of Vitamin D (VitD3). Taken together, this study demonstrates that in addition to its antimicrobial properties, LL-37 has immunomodulatory properties in the curse of DENV infection and its production can be increased by VitD3.COL001244411application/pdfengOxford University PressOxford, Estados Unidoshttp://creativecommons.org/licenses/by-nc-sa/2.5/co/https://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessAtribución-NoComercial-CompartirIgual 2.5 Colombiahttp://purl.org/coar/access_right/c_abf2Vitamin D-induced LL-37 modulates innate immune responses of human primary macrophages during DENV-2 infectionArtículo de investigaciónhttp://purl.org/coar/resource_type/c_2df8fbb1https://purl.org/redcol/resource_type/ARTinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionVirus del DengueDengue VirusMacrófagosMacrophagesInmunidad InnataImmunity, InnateVitamina DVitamin DLL-37Pathog. 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