Cargando…

Salmonella Typhi Colonization Provokes Extensive Transcriptional Changes Aimed at Evading Host Mucosal Immune Defense During Early Infection of Human Intestinal Tissue

Commensal microorganisms influence a variety of host functions in the gut, including immune response, glucose homeostasis, metabolic pathways and oxidative stress, among others. This study describes how Salmonella Typhi, the pathogen responsible for typhoid fever, uses similar strategies to escape i...

Descripción completa

Detalles Bibliográficos
Autores principales: Nickerson, K.P., Senger, S., Zhang, Y., Lima, R., Patel, S., Ingano, L., Flavahan, W.A., Kumar, D.K.V., Fraser, C.M., Faherty, C.S., Sztein, M.B., Fiorentino, M., Fasano, A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013756/
https://www.ncbi.nlm.nih.gov/pubmed/29735417
http://dx.doi.org/10.1016/j.ebiom.2018.04.005
_version_ 1783334079043731456
author Nickerson, K.P.
Senger, S.
Zhang, Y.
Lima, R.
Patel, S.
Ingano, L.
Flavahan, W.A.
Kumar, D.K.V.
Fraser, C.M.
Faherty, C.S.
Sztein, M.B.
Fiorentino, M.
Fasano, A.
author_facet Nickerson, K.P.
Senger, S.
Zhang, Y.
Lima, R.
Patel, S.
Ingano, L.
Flavahan, W.A.
Kumar, D.K.V.
Fraser, C.M.
Faherty, C.S.
Sztein, M.B.
Fiorentino, M.
Fasano, A.
author_sort Nickerson, K.P.
collection PubMed
description Commensal microorganisms influence a variety of host functions in the gut, including immune response, glucose homeostasis, metabolic pathways and oxidative stress, among others. This study describes how Salmonella Typhi, the pathogen responsible for typhoid fever, uses similar strategies to escape immune defense responses and survive within its human host. To elucidate the early mechanisms of typhoid fever, we performed studies using healthy human intestinal tissue samples and “mini-guts,” organoids grown from intestinal tissue taken from biopsy specimens. We analyzed gene expression changes in human intestinal specimens and bacterial cells both separately and after colonization. Our results showed mechanistic strategies that S. Typhi uses to rearrange the cellular machinery of the host cytoskeleton to successfully invade the intestinal epithelium, promote polarized cytokine release and evade immune system activation by downregulating genes involved in antigen sampling and presentation during infection. This work adds novel information regarding S. Typhi infection pathogenesis in humans, by replicating work shown in traditional cell models, and providing new data that can be applied to future vaccine development strategies.
format Online
Article
Text
id pubmed-6013756
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-60137562018-06-26 Salmonella Typhi Colonization Provokes Extensive Transcriptional Changes Aimed at Evading Host Mucosal Immune Defense During Early Infection of Human Intestinal Tissue Nickerson, K.P. Senger, S. Zhang, Y. Lima, R. Patel, S. Ingano, L. Flavahan, W.A. Kumar, D.K.V. Fraser, C.M. Faherty, C.S. Sztein, M.B. Fiorentino, M. Fasano, A. EBioMedicine Research Paper Commensal microorganisms influence a variety of host functions in the gut, including immune response, glucose homeostasis, metabolic pathways and oxidative stress, among others. This study describes how Salmonella Typhi, the pathogen responsible for typhoid fever, uses similar strategies to escape immune defense responses and survive within its human host. To elucidate the early mechanisms of typhoid fever, we performed studies using healthy human intestinal tissue samples and “mini-guts,” organoids grown from intestinal tissue taken from biopsy specimens. We analyzed gene expression changes in human intestinal specimens and bacterial cells both separately and after colonization. Our results showed mechanistic strategies that S. Typhi uses to rearrange the cellular machinery of the host cytoskeleton to successfully invade the intestinal epithelium, promote polarized cytokine release and evade immune system activation by downregulating genes involved in antigen sampling and presentation during infection. This work adds novel information regarding S. Typhi infection pathogenesis in humans, by replicating work shown in traditional cell models, and providing new data that can be applied to future vaccine development strategies. Elsevier 2018-04-12 /pmc/articles/PMC6013756/ /pubmed/29735417 http://dx.doi.org/10.1016/j.ebiom.2018.04.005 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Nickerson, K.P.
Senger, S.
Zhang, Y.
Lima, R.
Patel, S.
Ingano, L.
Flavahan, W.A.
Kumar, D.K.V.
Fraser, C.M.
Faherty, C.S.
Sztein, M.B.
Fiorentino, M.
Fasano, A.
Salmonella Typhi Colonization Provokes Extensive Transcriptional Changes Aimed at Evading Host Mucosal Immune Defense During Early Infection of Human Intestinal Tissue
title Salmonella Typhi Colonization Provokes Extensive Transcriptional Changes Aimed at Evading Host Mucosal Immune Defense During Early Infection of Human Intestinal Tissue
title_full Salmonella Typhi Colonization Provokes Extensive Transcriptional Changes Aimed at Evading Host Mucosal Immune Defense During Early Infection of Human Intestinal Tissue
title_fullStr Salmonella Typhi Colonization Provokes Extensive Transcriptional Changes Aimed at Evading Host Mucosal Immune Defense During Early Infection of Human Intestinal Tissue
title_full_unstemmed Salmonella Typhi Colonization Provokes Extensive Transcriptional Changes Aimed at Evading Host Mucosal Immune Defense During Early Infection of Human Intestinal Tissue
title_short Salmonella Typhi Colonization Provokes Extensive Transcriptional Changes Aimed at Evading Host Mucosal Immune Defense During Early Infection of Human Intestinal Tissue
title_sort salmonella typhi colonization provokes extensive transcriptional changes aimed at evading host mucosal immune defense during early infection of human intestinal tissue
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013756/
https://www.ncbi.nlm.nih.gov/pubmed/29735417
http://dx.doi.org/10.1016/j.ebiom.2018.04.005
work_keys_str_mv AT nickersonkp salmonellatyphicolonizationprovokesextensivetranscriptionalchangesaimedatevadinghostmucosalimmunedefenseduringearlyinfectionofhumanintestinaltissue
AT sengers salmonellatyphicolonizationprovokesextensivetranscriptionalchangesaimedatevadinghostmucosalimmunedefenseduringearlyinfectionofhumanintestinaltissue
AT zhangy salmonellatyphicolonizationprovokesextensivetranscriptionalchangesaimedatevadinghostmucosalimmunedefenseduringearlyinfectionofhumanintestinaltissue
AT limar salmonellatyphicolonizationprovokesextensivetranscriptionalchangesaimedatevadinghostmucosalimmunedefenseduringearlyinfectionofhumanintestinaltissue
AT patels salmonellatyphicolonizationprovokesextensivetranscriptionalchangesaimedatevadinghostmucosalimmunedefenseduringearlyinfectionofhumanintestinaltissue
AT inganol salmonellatyphicolonizationprovokesextensivetranscriptionalchangesaimedatevadinghostmucosalimmunedefenseduringearlyinfectionofhumanintestinaltissue
AT flavahanwa salmonellatyphicolonizationprovokesextensivetranscriptionalchangesaimedatevadinghostmucosalimmunedefenseduringearlyinfectionofhumanintestinaltissue
AT kumardkv salmonellatyphicolonizationprovokesextensivetranscriptionalchangesaimedatevadinghostmucosalimmunedefenseduringearlyinfectionofhumanintestinaltissue
AT frasercm salmonellatyphicolonizationprovokesextensivetranscriptionalchangesaimedatevadinghostmucosalimmunedefenseduringearlyinfectionofhumanintestinaltissue
AT fahertycs salmonellatyphicolonizationprovokesextensivetranscriptionalchangesaimedatevadinghostmucosalimmunedefenseduringearlyinfectionofhumanintestinaltissue
AT szteinmb salmonellatyphicolonizationprovokesextensivetranscriptionalchangesaimedatevadinghostmucosalimmunedefenseduringearlyinfectionofhumanintestinaltissue
AT fiorentinom salmonellatyphicolonizationprovokesextensivetranscriptionalchangesaimedatevadinghostmucosalimmunedefenseduringearlyinfectionofhumanintestinaltissue
AT fasanoa salmonellatyphicolonizationprovokesextensivetranscriptionalchangesaimedatevadinghostmucosalimmunedefenseduringearlyinfectionofhumanintestinaltissue