Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1782434605338460160 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4886356 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT blohmkechristophj interferondrivenalterationsofthehostsaminoacidmetabolisminthepathogenesisoftyphoidfever AT dartonthomasc interferondrivenalterationsofthehostsaminoacidmetabolisminthepathogenesisoftyphoidfever AT jonesclaire interferondrivenalterationsofthehostsaminoacidmetabolisminthepathogenesisoftyphoidfever AT suareznicolasm interferondrivenalterationsofthehostsaminoacidmetabolisminthepathogenesisoftyphoidfever AT waddingtonclaires interferondrivenalterationsofthehostsaminoacidmetabolisminthepathogenesisoftyphoidfever AT angusbrian interferondrivenalterationsofthehostsaminoacidmetabolisminthepathogenesisoftyphoidfever AT zhouliqing interferondrivenalterationsofthehostsaminoacidmetabolisminthepathogenesisoftyphoidfever AT hilljennifer interferondrivenalterationsofthehostsaminoacidmetabolisminthepathogenesisoftyphoidfever AT claresimon interferondrivenalterationsofthehostsaminoacidmetabolisminthepathogenesisoftyphoidfever AT kaneleanne interferondrivenalterationsofthehostsaminoacidmetabolisminthepathogenesisoftyphoidfever AT mukhopadhyaysubhankar interferondrivenalterationsofthehostsaminoacidmetabolisminthepathogenesisoftyphoidfever AT schreiberfernanda interferondrivenalterationsofthehostsaminoacidmetabolisminthepathogenesisoftyphoidfever AT duquecorreamariaa interferondrivenalterationsofthehostsaminoacidmetabolisminthepathogenesisoftyphoidfever AT wrightjamesc interferondrivenalterationsofthehostsaminoacidmetabolisminthepathogenesisoftyphoidfever AT roumeliotistheodorosi interferondrivenalterationsofthehostsaminoacidmetabolisminthepathogenesisoftyphoidfever AT yulu interferondrivenalterationsofthehostsaminoacidmetabolisminthepathogenesisoftyphoidfever AT choudharyjyotis interferondrivenalterationsofthehostsaminoacidmetabolisminthepathogenesisoftyphoidfever AT mejiasasuncion interferondrivenalterationsofthehostsaminoacidmetabolisminthepathogenesisoftyphoidfever AT ramilooctavio interferondrivenalterationsofthehostsaminoacidmetabolisminthepathogenesisoftyphoidfever AT shanyindemilensu interferondrivenalterationsofthehostsaminoacidmetabolisminthepathogenesisoftyphoidfever AT szteinmarcelob interferondrivenalterationsofthehostsaminoacidmetabolisminthepathogenesisoftyphoidfever AT kingsleyroberta interferondrivenalterationsofthehostsaminoacidmetabolisminthepathogenesisoftyphoidfever AT lockhartstephen interferondrivenalterationsofthehostsaminoacidmetabolisminthepathogenesisoftyphoidfever AT levinemyronm interferondrivenalterationsofthehostsaminoacidmetabolisminthepathogenesisoftyphoidfever AT lynndavidj interferondrivenalterationsofthehostsaminoacidmetabolisminthepathogenesisoftyphoidfever AT dougangordon interferondrivenalterationsofthehostsaminoacidmetabolisminthepathogenesisoftyphoidfever AT pollardandrewj interferondrivenalterationsofthehostsaminoacidmetabolisminthepathogenesisoftyphoidfever |