Salmonella Typhi Colonization Provokes Extensive Transcriptional Changes Aimed at Evading Host Mucosal Immune Defense During Early Infection of Human Intestinal Tissue
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2018-05-01Journal
EBioMedicinePublisher
Elsevier B.V.Type
Article
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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. © 2018 The AuthorsSponsors
These studies were supported, in part, by NIAID, NIH, DHHS grants R01-AI036525 (to MBS), U19-AI082655 [Cooperative Center on Human Immunology] (to MBS and AF), and U19-AI109776 [Center of Excellence for Translational Research (CETR)] to MBS.Keyword
Host-pathogen interactionHuman tissue
Immune evasion
Immune system
Innate immunity
Intestinal organoids
Organoid monolayer
Salmonella
Snapwell™ system
Terminal ileum
Typhoid fever
Vaccine development
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https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85046687462&origin=inward; http://hdl.handle.net/10713/9847ae974a485f413a2113503eed53cd6c53
10.1016/j.ebiom.2018.04.005
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