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Japanese Encephalitis Virus Induce Immuno-Competency in Neural Stem/Progenitor Cells

BACKGROUND: The low immunogenicity of neural stem/progenitor cells (NSPCs) coupled with negligible expression of MHC antigens has popularized their use in transplantation medicine. However, in an inflammatory environment, the NSPCs express costimulatory molecules and MHC antigens, and also exhibit c...

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Autores principales: Das, Sulagna, Ghosh, Debapriya, Basu, Anirban
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2780913/
https://www.ncbi.nlm.nih.gov/pubmed/19956550
http://dx.doi.org/10.1371/journal.pone.0008134
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author Das, Sulagna
Ghosh, Debapriya
Basu, Anirban
author_facet Das, Sulagna
Ghosh, Debapriya
Basu, Anirban
author_sort Das, Sulagna
collection PubMed
description BACKGROUND: The low immunogenicity of neural stem/progenitor cells (NSPCs) coupled with negligible expression of MHC antigens has popularized their use in transplantation medicine. However, in an inflammatory environment, the NSPCs express costimulatory molecules and MHC antigens, and also exhibit certain immunomodulatory functions. Since NSPCs are the cellular targets in a number of virus infections both during postnatal and adult stages, we wanted to investigate the immunological properties of these stem cells in response to viral pathogen. METHODOLOGY/PRINCIPAL FINDINGS: We utilized both in vivo mouse model and in vitro neurosphere model of Japanese encephalitis virus (JEV) infection for the study. The NSPCs residing in the subventricular zone of the infected brains showed prominent expression of MHC-I and costimulatory molecules CD40, CD80, and CD86. Using Flow cytometry and fluorescence microscopy, we observed increased surface expression of co-stimulatory molecule and MHC class I antigen in NSPCs upon progressive JEV infection in vitro. Moreover, significant production of pro-inflammatory cyto/chemokines was detected in JEV infected NSPCs by Cytokine Bead Array analysis. Interestingly, NSPCs were capable of providing functional costimulation to allogenic T cells and JEV infection resulted in increased proliferation of allogenic T cells, as detected by Mixed Lymphocyte reaction and CFSE experiments. We also report IL-2 production by NSPCs upon JEV infection, which possibly provides mitogenic signals to T cells and trigger their proliferation. CONCLUSION/SIGNIFICANCE: The in vivo and in vitro findings clearly indicate the development of immunogenicity in NSPCs following progressive JEV infection, in our case, JEV infection. Following a neurotropic virus infection, NSPCs possibly behave as immunogenic cells and contribute to both the innate and adaptive immune axes. The newly discovered immunological properties of NSPCs may have implications in assigning a new role of these cells as non-professional antigen presenting cells in the central nervous system.
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spelling pubmed-27809132009-12-03 Japanese Encephalitis Virus Induce Immuno-Competency in Neural Stem/Progenitor Cells Das, Sulagna Ghosh, Debapriya Basu, Anirban PLoS One Research Article BACKGROUND: The low immunogenicity of neural stem/progenitor cells (NSPCs) coupled with negligible expression of MHC antigens has popularized their use in transplantation medicine. However, in an inflammatory environment, the NSPCs express costimulatory molecules and MHC antigens, and also exhibit certain immunomodulatory functions. Since NSPCs are the cellular targets in a number of virus infections both during postnatal and adult stages, we wanted to investigate the immunological properties of these stem cells in response to viral pathogen. METHODOLOGY/PRINCIPAL FINDINGS: We utilized both in vivo mouse model and in vitro neurosphere model of Japanese encephalitis virus (JEV) infection for the study. The NSPCs residing in the subventricular zone of the infected brains showed prominent expression of MHC-I and costimulatory molecules CD40, CD80, and CD86. Using Flow cytometry and fluorescence microscopy, we observed increased surface expression of co-stimulatory molecule and MHC class I antigen in NSPCs upon progressive JEV infection in vitro. Moreover, significant production of pro-inflammatory cyto/chemokines was detected in JEV infected NSPCs by Cytokine Bead Array analysis. Interestingly, NSPCs were capable of providing functional costimulation to allogenic T cells and JEV infection resulted in increased proliferation of allogenic T cells, as detected by Mixed Lymphocyte reaction and CFSE experiments. We also report IL-2 production by NSPCs upon JEV infection, which possibly provides mitogenic signals to T cells and trigger their proliferation. CONCLUSION/SIGNIFICANCE: The in vivo and in vitro findings clearly indicate the development of immunogenicity in NSPCs following progressive JEV infection, in our case, JEV infection. Following a neurotropic virus infection, NSPCs possibly behave as immunogenic cells and contribute to both the innate and adaptive immune axes. The newly discovered immunological properties of NSPCs may have implications in assigning a new role of these cells as non-professional antigen presenting cells in the central nervous system. Public Library of Science 2009-12-02 /pmc/articles/PMC2780913/ /pubmed/19956550 http://dx.doi.org/10.1371/journal.pone.0008134 Text en Das et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Das, Sulagna
Ghosh, Debapriya
Basu, Anirban
Japanese Encephalitis Virus Induce Immuno-Competency in Neural Stem/Progenitor Cells
title Japanese Encephalitis Virus Induce Immuno-Competency in Neural Stem/Progenitor Cells
title_full Japanese Encephalitis Virus Induce Immuno-Competency in Neural Stem/Progenitor Cells
title_fullStr Japanese Encephalitis Virus Induce Immuno-Competency in Neural Stem/Progenitor Cells
title_full_unstemmed Japanese Encephalitis Virus Induce Immuno-Competency in Neural Stem/Progenitor Cells
title_short Japanese Encephalitis Virus Induce Immuno-Competency in Neural Stem/Progenitor Cells
title_sort japanese encephalitis virus induce immuno-competency in neural stem/progenitor cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2780913/
https://www.ncbi.nlm.nih.gov/pubmed/19956550
http://dx.doi.org/10.1371/journal.pone.0008134
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