{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T21:09:46Z","timestamp":1790975386719,"version":"4.1.0"},"reference-count":96,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2020,5,1]],"date-time":"2020-05-01T00:00:00Z","timestamp":1588291200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Mitacs Accelerate Program","award":["IT15498"],"award-info":[{"award-number":["IT15498"]}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2017-05237"],"award-info":[{"award-number":["RGPIN-2017-05237"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Recent evidence suggests that lactic acid bacteria communicate with host cells via secretome components to influence immune responses but less is known about gut-pathogen secretomes, impact of lactic acid bacteria secretomes on host\u2013pathogen interactions, and the mechanisms underlying these interactions. Genome-wide microarrays and cytokine profiling were used to interrogate the impact of the Lactobacillus rhamnosus R0011 secretome (LrS) on TNF-\u03b1 and Salmonella enterica subsp. enterica serovar Typhimurium secretome (STS)\u2013induced outcomes in human intestinal epithelial cells. The LrS attenuated both TNF-\u03b1\u2013 and STS-induced gene expression involved in NF-\u03baB and MAPK activation, as well as expression of genes involved in other immune-related signaling pathways. Specifically, the LrS induced the expression of dual specificity phosphatase 1 (DUSP1), activating transcription factor 3 (ATF3), and tribbles pseudokinase 3 (TRIB3), negative regulators of innate immune signaling, in HT-29 intestinal epithelial cells challenged with TNF-\u03b1 or STS. TNF-\u03b1\u2013 and STS-induced acetylation of H3 and H4 histones was attenuated by the LrS, as was the production of TNF-\u03b1\u2013 and STS-induced proinflammatory cytokines and chemokines. Interestingly, the LrS induced production of macrophage migration inhibitory factor (MIF), a cytokine involved in host\u2013microbe interactions at the gut interface. We propose that the LrS attenuates proinflammatory mediator expression through increased transcription of negative regulators of innate immune activity and changes in global H3 and H4 histone acetylation. To our knowledge, these findings provide novel insights into the complex multifaceted mechanisms of action behind secretome-mediated interdomain communication at the gut-mucosal interface.<\/jats:p>","DOI":"10.4049\/jimmunol.1901440","type":"journal-article","created":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T20:24:28Z","timestamp":1585772668000},"page":"2523-2534","source":"Crossref","is-referenced-by-count":19,"title":["Secretome-Mediated Interactions with Intestinal Epithelial Cells: A Role for Secretome Components from <i>Lactobacillus rhamnosus<\/i> R0011 in the Attenuation of <i>Salmonella enterica<\/i> Serovar Typhimurium Secretome and TNF-\u03b1\u2013Induced Proinflammatory Responses"],"prefix":"10.1093","volume":"204","author":[{"given":"Michael P","family":"Jeffrey","sequence":"first","affiliation":[{"name":"Applied Bioscience Graduate Program and the Faculty of Science, Ontario Technical University , Oshawa, Ontario L1G 0C5 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad W","family":"MacPherson","sequence":"additional","affiliation":[{"name":"Rosell Institute for Microbiome and Probiotics , Montreal, Quebec H4P 2R2 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Mathieu","sequence":"additional","affiliation":[{"name":"Rosell Institute for Microbiome and Probiotics , Montreal, Quebec H4P 2R2 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2990-2265","authenticated-orcid":false,"given":"Thomas A","family":"Tompkins","sequence":"additional","affiliation":[{"name":"Rosell Institute for Microbiome and Probiotics , Montreal, Quebec H4P 2R2 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7207-2431","authenticated-orcid":false,"given":"Julia M","family":"Green-Johnson","sequence":"additional","affiliation":[{"name":"Applied Bioscience Graduate Program and the Faculty of Science, Ontario Technical University , Oshawa, Ontario L1G 0C5 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,5,1]]},"reference":[{"key":"2025030417511712800_r1","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1038\/s41591-019-0439-x","article-title":"The pros, cons, and many unknowns of probiotics","volume":"25","author":"Suez","year":"2019","journal-title":"Nat. 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