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Gastrointestinal Microbiome Dysbiosis in Infant Mice Alters Peripheral CD8(+) T Cell Receptor Signaling
We recently reported that maternal antibiotic treatment (MAT) of mice in the last days of pregnancy and during lactation dramatically alters the density and composition of the gastrointestinal microbiota of their infants. MAT infants also exhibited enhanced susceptibility to a systemic viral infecti...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2017
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340779/ https://www.ncbi.nlm.nih.gov/pubmed/28337207 http://dx.doi.org/10.3389/fimmu.2017.00265 |
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author | Gonzalez-Perez, Gabriela Lamousé-Smith, Esi S. N. |
author_facet | Gonzalez-Perez, Gabriela Lamousé-Smith, Esi S. N. |
author_sort | Gonzalez-Perez, Gabriela |
collection | PubMed |
description | We recently reported that maternal antibiotic treatment (MAT) of mice in the last days of pregnancy and during lactation dramatically alters the density and composition of the gastrointestinal microbiota of their infants. MAT infants also exhibited enhanced susceptibility to a systemic viral infection and altered adaptive immune cell activation phenotype and function. CD8(+) effector T cells from MAT infants consistently demonstrate an inability to sustain interferon gamma (IFN-γ) production in vivo following vaccinia virus infection and in vitro upon T cell receptor (TCR) stimulation. We hypothesize that T cells developing in infant mice with gastrointestinal microbiota dysbiosis and insufficient toll-like receptor (TLR) exposure alters immune responsiveness associated with intrinsic T cell defects in the TCR signaling pathway and compromised T cell effector function. To evaluate this, splenic T cells from day of life 15 MAT infant mice were stimulated in vitro with anti-CD3 and anti-CD28 antibodies prior to examining the expression of ZAP-70, phosphorylated ZAP-70, phospho-Erk-1/2, c-Rel, total protein tyrosine phosphorylation, and IFN-γ production. We determine that MAT infant CD8(+) T cells fail to sustain total protein tyrosine phosphorylation and Erk1/2 activation. Lipopolysaccharide treatment in vitro and in vivo, partially restored IFN-γ production in MAT effector CD8(+) T cells and reduced mortality typically observed in MAT mice following systemic viral infection. Our results demonstrate a surprising dependence on the gastrointestinal microbiome and TLR ligand stimulation toward shaping optimal CD8(+) T cell function during infancy. |
format | Online Article Text |
id | pubmed-5340779 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-53407792017-03-23 Gastrointestinal Microbiome Dysbiosis in Infant Mice Alters Peripheral CD8(+) T Cell Receptor Signaling Gonzalez-Perez, Gabriela Lamousé-Smith, Esi S. N. Front Immunol Immunology We recently reported that maternal antibiotic treatment (MAT) of mice in the last days of pregnancy and during lactation dramatically alters the density and composition of the gastrointestinal microbiota of their infants. MAT infants also exhibited enhanced susceptibility to a systemic viral infection and altered adaptive immune cell activation phenotype and function. CD8(+) effector T cells from MAT infants consistently demonstrate an inability to sustain interferon gamma (IFN-γ) production in vivo following vaccinia virus infection and in vitro upon T cell receptor (TCR) stimulation. We hypothesize that T cells developing in infant mice with gastrointestinal microbiota dysbiosis and insufficient toll-like receptor (TLR) exposure alters immune responsiveness associated with intrinsic T cell defects in the TCR signaling pathway and compromised T cell effector function. To evaluate this, splenic T cells from day of life 15 MAT infant mice were stimulated in vitro with anti-CD3 and anti-CD28 antibodies prior to examining the expression of ZAP-70, phosphorylated ZAP-70, phospho-Erk-1/2, c-Rel, total protein tyrosine phosphorylation, and IFN-γ production. We determine that MAT infant CD8(+) T cells fail to sustain total protein tyrosine phosphorylation and Erk1/2 activation. Lipopolysaccharide treatment in vitro and in vivo, partially restored IFN-γ production in MAT effector CD8(+) T cells and reduced mortality typically observed in MAT mice following systemic viral infection. Our results demonstrate a surprising dependence on the gastrointestinal microbiome and TLR ligand stimulation toward shaping optimal CD8(+) T cell function during infancy. Frontiers Media S.A. 2017-03-08 /pmc/articles/PMC5340779/ /pubmed/28337207 http://dx.doi.org/10.3389/fimmu.2017.00265 Text en Copyright © 2017 Gonzalez-Perez and Lamousé-Smith. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Gonzalez-Perez, Gabriela Lamousé-Smith, Esi S. N. Gastrointestinal Microbiome Dysbiosis in Infant Mice Alters Peripheral CD8(+) T Cell Receptor Signaling |
title | Gastrointestinal Microbiome Dysbiosis in Infant Mice Alters Peripheral CD8(+) T Cell Receptor Signaling |
title_full | Gastrointestinal Microbiome Dysbiosis in Infant Mice Alters Peripheral CD8(+) T Cell Receptor Signaling |
title_fullStr | Gastrointestinal Microbiome Dysbiosis in Infant Mice Alters Peripheral CD8(+) T Cell Receptor Signaling |
title_full_unstemmed | Gastrointestinal Microbiome Dysbiosis in Infant Mice Alters Peripheral CD8(+) T Cell Receptor Signaling |
title_short | Gastrointestinal Microbiome Dysbiosis in Infant Mice Alters Peripheral CD8(+) T Cell Receptor Signaling |
title_sort | gastrointestinal microbiome dysbiosis in infant mice alters peripheral cd8(+) t cell receptor signaling |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340779/ https://www.ncbi.nlm.nih.gov/pubmed/28337207 http://dx.doi.org/10.3389/fimmu.2017.00265 |
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