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

K. P. Nickerson, S. Senger, Y. Zhang, R. Lima, S. Patel, L. Ingano, W. A. Flavahan, D. K.V. Kumar, C. M. Fraser, C. S. Faherty, M. B. Sztein, M. Fiorentino, A. Fasano

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)92-109
Number of pages18
JournalEBioMedicine
Volume31
DOIs
StatePublished - May 2018
Externally publishedYes

Keywords

  • Host-pathogen interaction
  • Human tissue
  • Immune evasion
  • Immune system
  • Innate immunity
  • Intestinal organoids
  • Organoid monolayer
  • Salmonella
  • Snapwell™ system
  • Terminal ileum
  • Typhoid fever
  • Vaccine development

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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