Immunomodulatory effects of mesenchymal stem cell-conditioned media on lipopolysaccharide of Vibrio cholerae as a vaccine candidate

Abstract Background Vibrio cholerae is the causative agent of cholera, which is commonly associated with high morbidity and mortality, and presents a major challenge to healthcare systems throughout the world. Lipopolysaccharide (LPS) is required for full protection against V. cholerae but can induc...

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Autores principales: Mahboube Bahroudi, Bita Bakhshi, Sara Soudi, Shahin Najar-peerayeh
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Publicado: BMC 2021
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LPS
Acceso en línea:https://doaj.org/article/d2a136b9d3f849d7b1b0e3851ad75473
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spelling oai:doaj.org-article:d2a136b9d3f849d7b1b0e3851ad754732021-11-07T12:07:32ZImmunomodulatory effects of mesenchymal stem cell-conditioned media on lipopolysaccharide of Vibrio cholerae as a vaccine candidate10.1186/s13287-021-02622-01757-6512https://doaj.org/article/d2a136b9d3f849d7b1b0e3851ad754732021-11-01T00:00:00Zhttps://doi.org/10.1186/s13287-021-02622-0https://doaj.org/toc/1757-6512Abstract Background Vibrio cholerae is the causative agent of cholera, which is commonly associated with high morbidity and mortality, and presents a major challenge to healthcare systems throughout the world. Lipopolysaccharide (LPS) is required for full protection against V. cholerae but can induce inflammation and septic shock. Mesenchymal stem cells (MSCs) are currently used to treat infectious and inflammatory diseases. Therefore, this study aimed to evaluate the immune-modulating effects of the LPS‐MSC‐conditioned medium (CM) on V. cholerae LPS immunization in a murine model. Methods After preconditioning MSCs with LPS, mice were immunized intraperitoneally on days 0 and 14 with the following combinations: LPS + LPS-MSC-CM; detoxified LPS (DLPS) + MSC-CM; LPS + MSC sup; LPS; LPS-MSC-CM; MSC supernatant (MSC sup); and PBS. The mouse serum and saliva samples were collected to evaluate antibody (serum IgG and saliva IgA) and cytokine responses (TNF-α, IL-10, IL-6, TGF-β, IL-4, IL-5, and B-cell activating factor (BAFF)). Results The LPS + LPS-MSC-CM significantly increased total IgG and IgA compared to other combinations (P < 0.001). TNF-α levels, in contrast to IL-10 and TGF-β, were reduced significantly in mice receiving the LPS + LPS-MSC-CM compared to mice receiving only LPS. IL-4, IL-5, and BAFF levels significantly increased in mice receiving increased doses of LPS + LPS-MSC-CM compared to those who received only LPS. The highest vibriocidal antibody titer (1:64) was observed in LPS + LPS-MSC-CM-immunized mice and resulted in a significant improvement in survival in infant mice infected by V. cholerae O1. Conclusions The LPS-MSC-CM modulates the immune response to V. cholerae LPS by regulating inflammatory and anti-inflammatory responses and inducing vibriocidal antibodies, which protect neonate mice against V. cholerae infection.Mahboube BahroudiBita BakhshiSara SoudiShahin Najar-peerayehBMCarticleLPSVibrio choleraeMesenchymal stem cellsCytokineAntibodyMedicine (General)R5-920BiochemistryQD415-436ENStem Cell Research & Therapy, Vol 12, Iss 1, Pp 1-14 (2021)
institution DOAJ
collection DOAJ
language EN
topic LPS
Vibrio cholerae
Mesenchymal stem cells
Cytokine
Antibody
Medicine (General)
R5-920
Biochemistry
QD415-436
spellingShingle LPS
Vibrio cholerae
Mesenchymal stem cells
Cytokine
Antibody
Medicine (General)
R5-920
Biochemistry
QD415-436
Mahboube Bahroudi
Bita Bakhshi
Sara Soudi
Shahin Najar-peerayeh
Immunomodulatory effects of mesenchymal stem cell-conditioned media on lipopolysaccharide of Vibrio cholerae as a vaccine candidate
description Abstract Background Vibrio cholerae is the causative agent of cholera, which is commonly associated with high morbidity and mortality, and presents a major challenge to healthcare systems throughout the world. Lipopolysaccharide (LPS) is required for full protection against V. cholerae but can induce inflammation and septic shock. Mesenchymal stem cells (MSCs) are currently used to treat infectious and inflammatory diseases. Therefore, this study aimed to evaluate the immune-modulating effects of the LPS‐MSC‐conditioned medium (CM) on V. cholerae LPS immunization in a murine model. Methods After preconditioning MSCs with LPS, mice were immunized intraperitoneally on days 0 and 14 with the following combinations: LPS + LPS-MSC-CM; detoxified LPS (DLPS) + MSC-CM; LPS + MSC sup; LPS; LPS-MSC-CM; MSC supernatant (MSC sup); and PBS. The mouse serum and saliva samples were collected to evaluate antibody (serum IgG and saliva IgA) and cytokine responses (TNF-α, IL-10, IL-6, TGF-β, IL-4, IL-5, and B-cell activating factor (BAFF)). Results The LPS + LPS-MSC-CM significantly increased total IgG and IgA compared to other combinations (P < 0.001). TNF-α levels, in contrast to IL-10 and TGF-β, were reduced significantly in mice receiving the LPS + LPS-MSC-CM compared to mice receiving only LPS. IL-4, IL-5, and BAFF levels significantly increased in mice receiving increased doses of LPS + LPS-MSC-CM compared to those who received only LPS. The highest vibriocidal antibody titer (1:64) was observed in LPS + LPS-MSC-CM-immunized mice and resulted in a significant improvement in survival in infant mice infected by V. cholerae O1. Conclusions The LPS-MSC-CM modulates the immune response to V. cholerae LPS by regulating inflammatory and anti-inflammatory responses and inducing vibriocidal antibodies, which protect neonate mice against V. cholerae infection.
format article
author Mahboube Bahroudi
Bita Bakhshi
Sara Soudi
Shahin Najar-peerayeh
author_facet Mahboube Bahroudi
Bita Bakhshi
Sara Soudi
Shahin Najar-peerayeh
author_sort Mahboube Bahroudi
title Immunomodulatory effects of mesenchymal stem cell-conditioned media on lipopolysaccharide of Vibrio cholerae as a vaccine candidate
title_short Immunomodulatory effects of mesenchymal stem cell-conditioned media on lipopolysaccharide of Vibrio cholerae as a vaccine candidate
title_full Immunomodulatory effects of mesenchymal stem cell-conditioned media on lipopolysaccharide of Vibrio cholerae as a vaccine candidate
title_fullStr Immunomodulatory effects of mesenchymal stem cell-conditioned media on lipopolysaccharide of Vibrio cholerae as a vaccine candidate
title_full_unstemmed Immunomodulatory effects of mesenchymal stem cell-conditioned media on lipopolysaccharide of Vibrio cholerae as a vaccine candidate
title_sort immunomodulatory effects of mesenchymal stem cell-conditioned media on lipopolysaccharide of vibrio cholerae as a vaccine candidate
publisher BMC
publishDate 2021
url https://doaj.org/article/d2a136b9d3f849d7b1b0e3851ad75473
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AT bitabakhshi immunomodulatoryeffectsofmesenchymalstemcellconditionedmediaonlipopolysaccharideofvibriocholeraeasavaccinecandidate
AT sarasoudi immunomodulatoryeffectsofmesenchymalstemcellconditionedmediaonlipopolysaccharideofvibriocholeraeasavaccinecandidate
AT shahinnajarpeerayeh immunomodulatoryeffectsofmesenchymalstemcellconditionedmediaonlipopolysaccharideofvibriocholeraeasavaccinecandidate
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