caa a22 4500 528782126 20190923032426.0 cr unu---uuuuu 180924e20120406xx s 000 0 eng 10.3929/ethz-b-000050369 doi 10.1371/journal.pone.0034812 doi (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/50369 Salmonella Transiently Reside in Luminal Neutrophils in the Inflamed Gut [Elektronische Daten] [Yvonne Loetscher, Andreas Wieser, Jette Lengefeld, Patrick Kaiser, Sören Schubert, Mathias Heikenwalder, Wolf-Dietrich; id_orcid 0000-0002-9892-6420 Hardt, Bärbel Stecher] PLoS ONE Open access ethresearch Background Enteric pathogens need to grow efficiently in the gut lumen in order to cause disease and ensure transmission. The interior of the gut forms a complex environment comprising the mucosal surface area and the inner gut lumen with epithelial cell debris and food particles. Recruitment of neutrophils to the intestinal lumen is a hallmark of non-typhoidal Salmonella enterica infections in humans. Here, we analyzed the interaction of gut luminal neutrophils with S. enterica serovar Typhimurium (S. Tm) in a mouse colitis model. Results Upon S. Tmwt infection, neutrophils transmigrate across the mucosa into the intestinal lumen. We detected a majority of pathogens associated with luminal neutrophils 20 hours after infection. Neutrophils are viable and actively engulf S. Tm, as demonstrated by live microscopy. Using S. Tm mutant strains defective in tissue invasion we show that pathogens are mostly taken up in the gut lumen at the epithelial barrier by luminal neutrophils. In these luminal neutrophils, S. Tm induces expression of genes typically required for its intracellular lifestyle such as siderophore production iroBCDE and the Salmonella pathogenicity island 2 encoded type three secretion system (TTSS-2). This shows that S. Tm at least transiently survives and responds to engulfment by gut luminal neutrophils. Gentamicin protection experiments suggest that the life-span of luminal neutrophils is limited and that S. Tm is subsequently released into the gut lumen. This "fast cycling” through the intracellular compartment of gut luminal neutrophils would explain the high fraction of TTSS-2 and iroBCDE expressing intra- and extracellular bacteria in the lumen of the infected gut. Conclusion In conclusion, live neutrophils recruited during acute S. Tm colitis engulf pathogens in the gut lumen and may thus actively engage in shaping the environment of pathogens and commensals in the inflamed gut. Creative Commons Attribution 3.0 Unported http://creativecommons.org/licenses/by/3.0 ethresearch Loetscher Yvonne joint author Wieser Andreas joint author Lengefeld Jette joint author Kaiser Patrick joint author Schubert Sören joint author Heikenwalder Mathias joint author Hardt Wolf-Dietrich; id_orcid 0000-0002-9892-6420 joint author Stecher Bärbel joint author PLoS ONE S.l. : Public Library of Science 7 (4), p. e34812 1932-6203 http://hdl.handle.net/20.500.11850/50369 text/html WWW-Backlink auf das Repository (Open access) 1 Journal Article ethresearch ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/50369 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 700 1- Loetscher Yvonne joint author ETHRESEARCH 700 1- Wieser Andreas joint author ETHRESEARCH 700 1- Lengefeld Jette joint author ETHRESEARCH 700 1- Kaiser Patrick joint author ETHRESEARCH 700 1- Schubert Sören joint author ETHRESEARCH 700 1- Heikenwalder Mathias joint author ETHRESEARCH 700 1- Hardt Wolf-Dietrich; id_orcid 0000-0002-9892-6420 joint author ETHRESEARCH 700 1- Stecher Bärbel joint author ETHRESEARCH 773 0- PLoS ONE S.l. : Public Library of Science 7 (4), p. e34812 1932-6203 BK010053 XK010053 XK010000 ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access