Cancer Stem Cell News
Cell Therapy News
Dermal Cell News
Endothelial Cell News
ESC & iPSC News
Extracellular Matrix News
Hematopoiesis News
Hepatic Cell News
Human Immunology News
Immune Regulation News
Intestinal Cell News
Mammary Cell News
Mesenchymal Cell News
Muscle Cell News
Neural Cell News
Organoid News
Pancreatic Cell News
Prostate Cell News
Pulmonary Cell NewsScientists used a human intestinal organoid model to define host transcriptional responses to S. Typhimurium infection, also determining host pathways dependent on Salmonella pathogenicity island- 1- and -2-encoded type 3 secretion systems
[mBio]
6445212 M5Q4TD9X items 1 apa 0 default asc 1 162501 https://www.stemcellsciencenews.com/wp-content/plugins/zotpress/
%7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3A%22zotpress-577137f121e693fa1ea75c26acb976ff%22%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22M5Q4TD9X%22%2C%22library%22%3A%7B%22id%22%3A6445212%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Lawrence%20et%20al.%22%2C%22parsedDate%22%3A%222021-06-29%22%2C%22numChildren%22%3A3%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ELawrence%2C%20A.-L.%20E.%2C%20Abuaita%2C%20B.%20H.%2C%20Berger%2C%20R.%20P.%2C%20Hill%2C%20D.%20R.%2C%20Huang%2C%20S.%2C%20Yadagiri%2C%20V.%20K.%2C%20Bons%2C%20B.%2C%20Fields%2C%20C.%2C%20Wobus%2C%20C.%20E.%2C%20Spence%2C%20J.%20R.%2C%20Young%2C%20V.%20B.%2C%20%26amp%3B%20O%26%23x2019%3BRiordan%2C%20M.%20X.%20%282021%29.%20Salmonella%20enterica%20Serovar%20Typhimurium%20SPI-1%20and%20SPI-2%20Shape%20the%20Global%20Transcriptional%20Landscape%20in%20a%20Human%20Intestinal%20Organoid%20Model%20System.%20%3Ci%3EMBio%3C%5C%2Fi%3E%2C%20%3Ci%3E12%3C%5C%2Fi%3E%283%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1128%5C%2FmBio.00399-21%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1128%5C%2FmBio.00399-21%3C%5C%2Fa%3E%20%3Ca%20title%3D%27Cite%20in%20RIS%20Format%27%20class%3D%27zp-CiteRIS%27%20href%3D%27https%3A%5C%2F%5C%2Fwww.stemcellsciencenews.com%5C%2Fwp-content%5C%2Fplugins%5C%2Fzotpress%5C%2Flib%5C%2Frequest%5C%2Frequest.cite.php%3Fapi_user_id%3D6445212%26amp%3Bitem_key%3DM5Q4TD9X%27%3ECite%3C%5C%2Fa%3E%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Salmonella%20enterica%20Serovar%20Typhimurium%20SPI-1%20and%20SPI-2%20Shape%20the%20Global%20Transcriptional%20Landscape%20in%20a%20Human%20Intestinal%20Organoid%20Model%20System%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Anna-Lisa%20E.%22%2C%22lastName%22%3A%22Lawrence%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Basel%20H.%22%2C%22lastName%22%3A%22Abuaita%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ryan%20P.%22%2C%22lastName%22%3A%22Berger%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22David%20R.%22%2C%22lastName%22%3A%22Hill%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sha%22%2C%22lastName%22%3A%22Huang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Veda%20K.%22%2C%22lastName%22%3A%22Yadagiri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Brooke%22%2C%22lastName%22%3A%22Bons%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Courtney%22%2C%22lastName%22%3A%22Fields%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Christiane%20E.%22%2C%22lastName%22%3A%22Wobus%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jason%20R.%22%2C%22lastName%22%3A%22Spence%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Vincent%20B.%22%2C%22lastName%22%3A%22Young%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mary%20X.%22%2C%22lastName%22%3A%22O%5Cu2019Riordan%22%7D%5D%2C%22abstractNote%22%3A%22The%20intestinal%20epithelium%20is%20a%20primary%20interface%20for%20engagement%20of%20the%20host%20response%20by%20foodborne%20pathogens%2C%20like%20Salmonella%20enterica%20Typhimurium.%20While%20the%20interaction%20of%20S.%20Typhimurium%20with%20the%20mammalian%20host%20has%20been%20well%20studied%20in%20transformed%20epithelial%20cell%20lines%20or%20in%20the%20complex%20intestinal%20environment%20in%20vivo%2C%20few%20tractable%20models%20recapitulate%20key%20features%20of%20the%20intestine.%20Human%20intestinal%20organoids%20%28HIOs%29%20contain%20a%20polarized%20epithelium%20with%20functionally%20differentiated%20cell%20subtypes%2C%20including%20enterocytes%20and%20goblet%20cells%20and%20a%20supporting%20mesenchymal%20cell%20layer.%20HIOs%20contain%20luminal%20space%20that%20supports%20bacterial%20replication%2C%20are%20more%20amenable%20to%20experimental%20manipulation%20than%20animals%20and%20are%20more%20reflective%20of%20physiological%20host%20responses.%20Here%2C%20we%20use%20the%20HIO%20model%20to%20define%20host%20transcriptional%20responses%20to%20S.%20Typhimurium%20infection%2C%20also%20determining%20host%20pathways%20dependent%20on%20Salmonella%20pathogenicity%20island-1%20%28SPI-1%29-%20and%20-2%20%28SPI-2%29-encoded%20type%203%20secretion%20systems%20%28T3SS%29.%20Consistent%20with%20prior%20findings%2C%20we%20find%20that%20S.%20Typhimurium%20strongly%20stimulates%20proinflammatory%20gene%20expression.%20Infection-induced%20cytokine%20gene%20expression%20was%20rapid%2C%20transient%2C%20and%20largely%20independent%20of%20SPI-1%20T3SS-mediated%20invasion%2C%20likely%20due%20to%20continued%20luminal%20stimulation.%20Notably%2C%20S.%20Typhimurium%20infection%20led%20to%20significant%20downregulation%20of%20host%20genes%20associated%20with%20cell%20cycle%20and%20DNA%20repair%2C%20leading%20to%20a%20reduction%20in%20cellular%20proliferation%2C%20dependent%20on%20SPI-1%20and%20SPI-2%20T3SS.%20The%20transcriptional%20profile%20of%20cell%20cycle-associated%20target%20genes%20implicates%20multiple%20miRNAs%20as%20mediators%20of%20S.%20Typhimurium-dependent%20cell%20cycle%20suppression.%20These%20findings%20from%20Salmonella-infected%20HIOs%20delineate%20common%20and%20distinct%20contributions%20of%20SPI-1%20and%20SPI-2%20T3SSs%20in%20inducing%20early%20host%20responses%20during%20enteric%20infection%20and%20reinforce%20host%20cell%20proliferation%20as%20a%20process%20targeted%20by%20Salmonella.%5CnIMPORTANCE%20Salmonella%20enterica%20serovar%20Typhimurium%20%28S.%20Typhimurium%29%20causes%20a%20significant%20health%20burden%20worldwide%2C%20yet%20host%20responses%20to%20initial%20stages%20of%20intestinal%20infection%20remain%20poorly%20understood.%20Due%20to%20differences%20in%20infection%20outcome%20between%20mice%20and%20humans%2C%20physiological%20human%20host%20responses%20driven%20by%20major%20virulence%20determinants%20of%20Salmonella%20have%20been%20more%20challenging%20to%20evaluate.%20Here%2C%20we%20use%20the%20three-dimensional%20human%20intestinal%20organoid%20model%20to%20define%20early%20responses%20to%20infection%20with%20wild-type%20S.%20Typhimurium%20and%20mutants%20defective%20in%20the%20SPI-1%20or%20SPI-2%20type-3%20secretion%20systems.%20While%20both%20secretion%20system%20mutants%20show%20defects%20in%20mouse%20models%20of%20oral%20Salmonella%20infection%2C%20the%20specific%20contributions%20of%20each%20secretion%20system%20are%20less%20well%20understood.%20We%20show%20that%20S.%20Typhimurium%20upregulates%20proinflammatory%20pathways%20independently%20of%20either%20secretion%20system%2C%20while%20the%20downregulation%20of%20the%20host%20cell%20cycle%20pathways%20relies%20on%20both%20SPI-1%20and%20SPI-2.%20These%20findings%20lay%20the%20groundwork%20for%20future%20studies%20investigating%20how%20SPI-1-%20and%20SPI-2-driven%20host%20responses%20affect%20infection%20outcome%20and%20show%20the%20potential%20of%20this%20model%20to%20study%20host-pathogen%20interactions%20with%20other%20serovars%20to%20understand%20how%20initial%20interactions%20with%20the%20intestinal%20epithelium%20may%20affect%20pathogenesis.%22%2C%22date%22%3A%222021%5C%2F06%5C%2F29%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1128%5C%2FmBio.00399-21%22%2C%22ISSN%22%3A%222150-7511%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fmbio.asm.org%5C%2Fcontent%5C%2F12%5C%2F3%5C%2Fe00399-21%22%2C%22collections%22%3A%5B%5D%2C%22dateModified%22%3A%222021-05-19T22%3A57%3A22Z%22%7D%7D%5D%7D
Lawrence, A.-L. E., Abuaita, B. H., Berger, R. P., Hill, D. R., Huang, S., Yadagiri, V. K., Bons, B., Fields, C., Wobus, C. E., Spence, J. R., Young, V. B., & O’Riordan, M. X. (2021). Salmonella enterica Serovar Typhimurium SPI-1 and SPI-2 Shape the Global Transcriptional Landscape in a Human Intestinal Organoid Model System. MBio, 12(3). https://doi.org/10.1128/mBio.00399-21 Cite
