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Age-Dependent Enterocyte Invasion and Microcolony Formation by


Non-typhoidal Salmonella are among of the most prevalent causative agents of infectious diarrheal disease worldwide but also very significantly contribute to infant sepsis and meningitis particularly in developing countries. The underlying mechanisms of the elevated susceptibility of the infant host to systemic Salmonella infection have not been investigated. Here we analyzed age-dependent differences in the colonization, mucosal translocation and systemic spread in a murine oral infection model. We observed efficient entry of Salmonella in intestinal epithelial cells of newborn mice. Enterocyte invasion was followed by massive bacterial proliferation and the formation of large intraepithelial bacterial colonies. Intraepithelial, but not non-invasive, extracellular Salmonella induced a potent immune stimulation. Also, enterocyte invasion was required for translocation through the mucosal barrier and spread of Salmonella to systemic organs. This requirement was due to the absence of M cells, specialized epithelial cells that forward luminal antigen to the underlying immune cells, in the neonate host. Our results identify age-dependent factors of host susceptibility and illustrate the initial phase of Salmonella infection. They further present a new small animal model amenable to genetic manipulation to investigate the interaction of this pathogen with epithelial cells and characterize the early steps in Salmonella pathogenesis.


Vyšlo v časopise: Age-Dependent Enterocyte Invasion and Microcolony Formation by. PLoS Pathog 10(9): e32767. doi:10.1371/journal.ppat.1004385
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004385

Souhrn

Non-typhoidal Salmonella are among of the most prevalent causative agents of infectious diarrheal disease worldwide but also very significantly contribute to infant sepsis and meningitis particularly in developing countries. The underlying mechanisms of the elevated susceptibility of the infant host to systemic Salmonella infection have not been investigated. Here we analyzed age-dependent differences in the colonization, mucosal translocation and systemic spread in a murine oral infection model. We observed efficient entry of Salmonella in intestinal epithelial cells of newborn mice. Enterocyte invasion was followed by massive bacterial proliferation and the formation of large intraepithelial bacterial colonies. Intraepithelial, but not non-invasive, extracellular Salmonella induced a potent immune stimulation. Also, enterocyte invasion was required for translocation through the mucosal barrier and spread of Salmonella to systemic organs. This requirement was due to the absence of M cells, specialized epithelial cells that forward luminal antigen to the underlying immune cells, in the neonate host. Our results identify age-dependent factors of host susceptibility and illustrate the initial phase of Salmonella infection. They further present a new small animal model amenable to genetic manipulation to investigate the interaction of this pathogen with epithelial cells and characterize the early steps in Salmonella pathogenesis.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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