Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.ppat.1004557
Title: Granulocytes Impose a Tight Bottleneck upon the Gut Luminal Pathogen Population during Salmonella Typhimurium Colitis
Authors: Maier L.
Diard M.
Sellin M.E.
Chouffane E.-S.
Trautwein-Weidner K.
Periaswamy B. 
Slack E.
Dolowschiak T.
Stecher B.
German Center for Infection Research (DZIF) Partner site Ludwig Maximilian University of Munich
Loverdo C.
Regoes R.R.
Keywords: reduced nicotinamide adenine dinucleotide phosphate oxidase
streptomycin
antiinfective agent
bacterial protein
membrane protein
SPI-2 protein, Salmonella
Spi1 protein, Salmonella
streptomycin
animal experiment
animal model
animal tissue
Article
bacterial growth
bacterial load
bacterium mutant
cecum
colitis
controlled study
flow cytometry
genetic variability
granulocyte
immunofluorescence test
inflammation
intestine flora
liver
mathematical model
mouse
nonhuman
real time polymerase chain reaction
Salmonella typhimurium
spleen
animal
C57BL mouse
colitis
disease model
female
gastrointestinal tract
genetics
granulocyte
growth, development and aging
male
metabolism
microbiology
microflora
mutation
pathology
physiology
Salmonella enterica serovar Typhimurium
Salmonella Infections, Animal
theoretical model
Mus
Salmonella
Salmonella typhimurium
Animals
Anti-Bacterial Agents
Bacterial Proteins
Cecum
Colitis
Disease Models, Animal
Female
Gastrointestinal Tract
Granulocytes
Male
Membrane Proteins
Mice
Mice, Inbred C57BL
Microbiota
Models, Theoretical
Mutation
Salmonella Infections, Animal
Salmonella typhimurium
Streptomycin
Issue Date: 2014
Citation: Maier L., Diard M., Sellin M.E., Chouffane E.-S., Trautwein-Weidner K., Periaswamy B., Slack E., Dolowschiak T., Stecher B., German Center for Infection Research (DZIF) Partner site Ludwig Maximilian University of Munich, Loverdo C., Regoes R.R. (2014). Granulocytes Impose a Tight Bottleneck upon the Gut Luminal Pathogen Population during Salmonella Typhimurium Colitis. PLoS Pathogens 10 (12) : Jan-17. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.ppat.1004557
Rights: Attribution 4.0 International
Abstract: Topological, chemical and immunological barriers are thought to limit infection by enteropathogenic bacteria. However, in many cases these barriers and their consequences for the infection process remain incompletely understood. Here, we employed a mouse model for Salmonella colitis and a mixed inoculum approach to identify barriers limiting the gut luminal pathogen population. Mice were infected via the oral route with wild type S. Typhimurium (S. Tm) and/or mixtures of phenotypically identical but differentially tagged S. Tm strains (?WITS?, wild-type isogenic tagged strains), which can be individually tracked by quantitative real-time PCR. WITS dilution experiments identified a substantial loss in tag/genetic diversity within the gut luminal S. Tm population by days 2?4 post infection. The diversity-loss was not attributable to overgrowth by S. Tm mutants, but required inflammation, Gr-1+ cells (mainly neutrophilic granulocytes) and most likely NADPH-oxidase-mediated defense, but not iNOS. Mathematical modelling indicated that inflammation inflicts a bottleneck transiently restricting the gut luminal S. Tm population to approximately 6000 cells and plating experiments verified a transient, inflammation- and Gr-1+ cell-dependent dip in the gut luminal S. Tm population at day 2 post infection. We conclude that granulocytes, an important clinical hallmark of S. Tm-induced inflammation, impose a drastic bottleneck upon the pathogen population. This extends the current view of inflammation-fuelled gut-luminal Salmonella growth by establishing the host response in the intestinal lumen as a double-edged sword, fostering and diminishing colonization in a dynamic equilibrium. Our work identifies a potent immune defense against gut infection and reveals a potential Achilles' heel of the infection process which might be targeted for therapy. ? 2014 Maier et al.
Source Title: PLoS Pathogens
URI: https://scholarbank.nus.edu.sg/handle/10635/161942
ISSN: 15537366
DOI: 10.1371/journal.ppat.1004557
Rights: Attribution 4.0 International
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