Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2.

A dysregulated or exacerbated inflammatory response is thought to be the key driver of the pathogenesis of severe disease caused by the mosquito-borne dengue virus (DENV). Compounds that restrict virus replication and modulate the inflammatory response could thus serve as promising therapeutics miti...

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Autores principales:	Jorge Andrés Castillo, Diana M Giraldo, Juan C Hernandez, Jolanda M Smit, Izabela A Rodenhuis-Zybert, Silvio Urcuqui-Inchima
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/63db230099ec4adf8a56a23c23246927
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spelling	oai:doaj.org-article:63db230099ec4adf8a56a23c232469272021-11-25T06:33:24ZRegulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2.1935-27271935-273510.1371/journal.pntd.0009873https://doaj.org/article/63db230099ec4adf8a56a23c232469272021-10-01T00:00:00Zhttps://doi.org/10.1371/journal.pntd.0009873https://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735A dysregulated or exacerbated inflammatory response is thought to be the key driver of the pathogenesis of severe disease caused by the mosquito-borne dengue virus (DENV). Compounds that restrict virus replication and modulate the inflammatory response could thus serve as promising therapeutics mitigating the disease pathogenesis. We and others have previously shown that macrophages, which are important cellular targets for DENV replication, differentiated in the presence of bioactive vitamin D (VitD3) are less permissive to viral replication, and produce lower levels of pro-inflammatory cytokines. Therefore, we here evaluated the extent and kinetics of innate immune responses of DENV-2 infected monocytes differentiated into macrophages in the presence (D3-MDMs) or absence of VitD3 (MDMs). We found that D3-MDMs expressed lower levels of RIG I, Toll-like receptor (TLR)3, and TLR7, as well as higher levels of SOCS-1 in response to DENV-2 infection. D3-MDMs produced lower levels of reactive oxygen species, related to a lower expression of TLR9. Moreover, although VitD3 treatment did not modulate either the expression of IFN-α or IFN-β, higher expression of protein kinase R (PKR) and 2'-5'-oligoadenylate synthetase 1 (OAS1) mRNA were found in D3-MDMs. Importantly, the observed effects were independent of reduced infection, highlighting the intrinsic differences between D3-MDMs and MDMs. Taken together, our results suggest that differentiation of MDMs in the presence of VitD3 modulates innate immunity in responses to DENV-2 infection.Jorge Andrés CastilloDiana M GiraldoJuan C HernandezJolanda M SmitIzabela A Rodenhuis-ZybertSilvio Urcuqui-InchimaPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 15, Iss 10, p e0009873 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
spellingShingle	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Jorge Andrés Castillo Diana M Giraldo Juan C Hernandez Jolanda M Smit Izabela A Rodenhuis-Zybert Silvio Urcuqui-Inchima Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2.
description	A dysregulated or exacerbated inflammatory response is thought to be the key driver of the pathogenesis of severe disease caused by the mosquito-borne dengue virus (DENV). Compounds that restrict virus replication and modulate the inflammatory response could thus serve as promising therapeutics mitigating the disease pathogenesis. We and others have previously shown that macrophages, which are important cellular targets for DENV replication, differentiated in the presence of bioactive vitamin D (VitD3) are less permissive to viral replication, and produce lower levels of pro-inflammatory cytokines. Therefore, we here evaluated the extent and kinetics of innate immune responses of DENV-2 infected monocytes differentiated into macrophages in the presence (D3-MDMs) or absence of VitD3 (MDMs). We found that D3-MDMs expressed lower levels of RIG I, Toll-like receptor (TLR)3, and TLR7, as well as higher levels of SOCS-1 in response to DENV-2 infection. D3-MDMs produced lower levels of reactive oxygen species, related to a lower expression of TLR9. Moreover, although VitD3 treatment did not modulate either the expression of IFN-α or IFN-β, higher expression of protein kinase R (PKR) and 2'-5'-oligoadenylate synthetase 1 (OAS1) mRNA were found in D3-MDMs. Importantly, the observed effects were independent of reduced infection, highlighting the intrinsic differences between D3-MDMs and MDMs. Taken together, our results suggest that differentiation of MDMs in the presence of VitD3 modulates innate immunity in responses to DENV-2 infection.
format	article
author	Jorge Andrés Castillo Diana M Giraldo Juan C Hernandez Jolanda M Smit Izabela A Rodenhuis-Zybert Silvio Urcuqui-Inchima
author_facet	Jorge Andrés Castillo Diana M Giraldo Juan C Hernandez Jolanda M Smit Izabela A Rodenhuis-Zybert Silvio Urcuqui-Inchima
author_sort	Jorge Andrés Castillo
title	Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2.
title_short	Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2.
title_full	Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2.
title_fullStr	Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2.
title_full_unstemmed	Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2.
title_sort	regulation of innate immune responses in macrophages differentiated in the presence of vitamin d and infected with dengue virus 2.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/63db230099ec4adf8a56a23c23246927
work_keys_str_mv	AT jorgeandrescastillo regulationofinnateimmuneresponsesinmacrophagesdifferentiatedinthepresenceofvitamindandinfectedwithdenguevirus2 AT dianamgiraldo regulationofinnateimmuneresponsesinmacrophagesdifferentiatedinthepresenceofvitamindandinfectedwithdenguevirus2 AT juanchernandez regulationofinnateimmuneresponsesinmacrophagesdifferentiatedinthepresenceofvitamindandinfectedwithdenguevirus2 AT jolandamsmit regulationofinnateimmuneresponsesinmacrophagesdifferentiatedinthepresenceofvitamindandinfectedwithdenguevirus2 AT izabelaarodenhuiszybert regulationofinnateimmuneresponsesinmacrophagesdifferentiatedinthepresenceofvitamindandinfectedwithdenguevirus2 AT silviourcuquiinchima regulationofinnateimmuneresponsesinmacrophagesdifferentiatedinthepresenceofvitamindandinfectedwithdenguevirus2
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Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2.

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