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Interferon-driven alterations of the host’s amino acid metabolism in the pathogenesis of typhoid fever

Enteric fever, caused by Salmonella enterica serovar Typhi, is an important public health problem in resource-limited settings and, despite decades of research, human responses to the infection are poorly understood. In 41 healthy adults experimentally infected with wild-type S. Typhi, we detected s...

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Autores principales: Blohmke, Christoph J., Darton, Thomas C., Jones, Claire, Suarez, Nicolas M., Waddington, Claire S., Angus, Brian, Zhou, Liqing, Hill, Jennifer, Clare, Simon, Kane, Leanne, Mukhopadhyay, Subhankar, Schreiber, Fernanda, Duque-Correa, Maria A., Wright, James C., Roumeliotis, Theodoros I., Yu, Lu, Choudhary, Jyoti S., Mejias, Asuncion, Ramilo, Octavio, Shanyinde, Milensu, Sztein, Marcelo B., Kingsley, Robert A., Lockhart, Stephen, Levine, Myron M., Lynn, David J., Dougan, Gordon, Pollard, Andrew J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886356/
https://www.ncbi.nlm.nih.gov/pubmed/27217537
http://dx.doi.org/10.1084/jem.20151025
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author Blohmke, Christoph J.
Darton, Thomas C.
Jones, Claire
Suarez, Nicolas M.
Waddington, Claire S.
Angus, Brian
Zhou, Liqing
Hill, Jennifer
Clare, Simon
Kane, Leanne
Mukhopadhyay, Subhankar
Schreiber, Fernanda
Duque-Correa, Maria A.
Wright, James C.
Roumeliotis, Theodoros I.
Yu, Lu
Choudhary, Jyoti S.
Mejias, Asuncion
Ramilo, Octavio
Shanyinde, Milensu
Sztein, Marcelo B.
Kingsley, Robert A.
Lockhart, Stephen
Levine, Myron M.
Lynn, David J.
Dougan, Gordon
Pollard, Andrew J.
author_facet Blohmke, Christoph J.
Darton, Thomas C.
Jones, Claire
Suarez, Nicolas M.
Waddington, Claire S.
Angus, Brian
Zhou, Liqing
Hill, Jennifer
Clare, Simon
Kane, Leanne
Mukhopadhyay, Subhankar
Schreiber, Fernanda
Duque-Correa, Maria A.
Wright, James C.
Roumeliotis, Theodoros I.
Yu, Lu
Choudhary, Jyoti S.
Mejias, Asuncion
Ramilo, Octavio
Shanyinde, Milensu
Sztein, Marcelo B.
Kingsley, Robert A.
Lockhart, Stephen
Levine, Myron M.
Lynn, David J.
Dougan, Gordon
Pollard, Andrew J.
author_sort Blohmke, Christoph J.
collection PubMed
description Enteric fever, caused by Salmonella enterica serovar Typhi, is an important public health problem in resource-limited settings and, despite decades of research, human responses to the infection are poorly understood. In 41 healthy adults experimentally infected with wild-type S. Typhi, we detected significant cytokine responses within 12 h of bacterial ingestion. These early responses did not correlate with subsequent clinical disease outcomes and likely indicate initial host–pathogen interactions in the gut mucosa. In participants developing enteric fever after oral infection, marked transcriptional and cytokine responses during acute disease reflected dominant type I/II interferon signatures, which were significantly associated with bacteremia. Using a murine and macrophage infection model, we validated the pivotal role of this response in the expression of proteins of the host tryptophan metabolism during Salmonella infection. Corresponding alterations in tryptophan catabolites with immunomodulatory properties in serum of participants with typhoid fever confirmed the activity of this pathway, and implicate a central role of host tryptophan metabolism in the pathogenesis of typhoid fever.
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spelling pubmed-48863562016-11-30 Interferon-driven alterations of the host’s amino acid metabolism in the pathogenesis of typhoid fever Blohmke, Christoph J. Darton, Thomas C. Jones, Claire Suarez, Nicolas M. Waddington, Claire S. Angus, Brian Zhou, Liqing Hill, Jennifer Clare, Simon Kane, Leanne Mukhopadhyay, Subhankar Schreiber, Fernanda Duque-Correa, Maria A. Wright, James C. Roumeliotis, Theodoros I. Yu, Lu Choudhary, Jyoti S. Mejias, Asuncion Ramilo, Octavio Shanyinde, Milensu Sztein, Marcelo B. Kingsley, Robert A. Lockhart, Stephen Levine, Myron M. Lynn, David J. Dougan, Gordon Pollard, Andrew J. J Exp Med Research Articles Enteric fever, caused by Salmonella enterica serovar Typhi, is an important public health problem in resource-limited settings and, despite decades of research, human responses to the infection are poorly understood. In 41 healthy adults experimentally infected with wild-type S. Typhi, we detected significant cytokine responses within 12 h of bacterial ingestion. These early responses did not correlate with subsequent clinical disease outcomes and likely indicate initial host–pathogen interactions in the gut mucosa. In participants developing enteric fever after oral infection, marked transcriptional and cytokine responses during acute disease reflected dominant type I/II interferon signatures, which were significantly associated with bacteremia. Using a murine and macrophage infection model, we validated the pivotal role of this response in the expression of proteins of the host tryptophan metabolism during Salmonella infection. Corresponding alterations in tryptophan catabolites with immunomodulatory properties in serum of participants with typhoid fever confirmed the activity of this pathway, and implicate a central role of host tryptophan metabolism in the pathogenesis of typhoid fever. The Rockefeller University Press 2016-05-30 /pmc/articles/PMC4886356/ /pubmed/27217537 http://dx.doi.org/10.1084/jem.20151025 Text en © 2016 Blohmke et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Blohmke, Christoph J.
Darton, Thomas C.
Jones, Claire
Suarez, Nicolas M.
Waddington, Claire S.
Angus, Brian
Zhou, Liqing
Hill, Jennifer
Clare, Simon
Kane, Leanne
Mukhopadhyay, Subhankar
Schreiber, Fernanda
Duque-Correa, Maria A.
Wright, James C.
Roumeliotis, Theodoros I.
Yu, Lu
Choudhary, Jyoti S.
Mejias, Asuncion
Ramilo, Octavio
Shanyinde, Milensu
Sztein, Marcelo B.
Kingsley, Robert A.
Lockhart, Stephen
Levine, Myron M.
Lynn, David J.
Dougan, Gordon
Pollard, Andrew J.
Interferon-driven alterations of the host’s amino acid metabolism in the pathogenesis of typhoid fever
title Interferon-driven alterations of the host’s amino acid metabolism in the pathogenesis of typhoid fever
title_full Interferon-driven alterations of the host’s amino acid metabolism in the pathogenesis of typhoid fever
title_fullStr Interferon-driven alterations of the host’s amino acid metabolism in the pathogenesis of typhoid fever
title_full_unstemmed Interferon-driven alterations of the host’s amino acid metabolism in the pathogenesis of typhoid fever
title_short Interferon-driven alterations of the host’s amino acid metabolism in the pathogenesis of typhoid fever
title_sort interferon-driven alterations of the host’s amino acid metabolism in the pathogenesis of typhoid fever
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886356/
https://www.ncbi.nlm.nih.gov/pubmed/27217537
http://dx.doi.org/10.1084/jem.20151025
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