{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T04:24:34Z","timestamp":1771561474309,"version":"3.50.1"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Serotonin (5-hydroxytryptamine [5-HT]) is a key enteric signaling molecule that mediates various physiological processes in the gut. Enterochromaffin (EC) cells in the mucosal layer of the gut are the main source of 5-HT in the body and are situated in close proximity to the gut microbiota. In this study, we identify a pivotal role of TLR2 in 5-HT production in the gut. Antibiotic treatment reduces EC cell numbers and 5-HT levels in naive C57BL\/6 mice, which is associated with downregulation of TLR2 expression but not TLR1 or TLR4. TLR2-deficient (Tlr2\u2212\/\u2212) and Myd88\u2212\/\u2212 mice express lower EC cell numbers and 5-HT levels, whereas treatment with TLR2\/1 agonist upregulates 5-HT production in irradiated C57BL\/6 mice, which are reconstituted with Tlr2\u2212\/\u2212 bone marrow cells, and in germ-free mice. Human EC cell line (BON-1 cells) release higher 5-HT upon TLR2\/1 agonist via NF-\u03baB pathway. Tlr2\u2212\/\u2212 mice and anti-TLR2 Ab\u2013treated mice infected with enteric parasite, Trichuris muris, exhibited attenuated 5-HT production, compared with infected wild-type mice. Moreover, excretory-secretory products from T. muris induce higher 5-HT production in BON-1 cells via TLR2 in a dose-dependent manner, whereby the effect of excretory-secretory products is abrogated by TLR2 antagonist. These findings not only suggest an important role of TLR2 in mucosal 5-HT production in the gut by resident microbiota as well as by a nematode parasite but also provide, to our knowledge, novel information on the potential benefits of targeting TLR2 in various gut disorders that exhibit aberrant 5-HT signaling.<\/jats:p>","DOI":"10.4049\/jimmunol.1801034","type":"journal-article","created":{"date-parts":[[2019,4,5]],"date-time":"2019-04-05T20:23:49Z","timestamp":1554495829000},"page":"3041-3052","source":"Crossref","is-referenced-by-count":42,"title":["TLR2 Plays a Pivotal Role in Mediating Mucosal Serotonin Production in the Gut"],"prefix":"10.1093","volume":"202","author":[{"given":"Huaqing","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pathology and Molecular Medicine, McMaster University , Hamilton, Ontario L8S 4K1 ,","place":["Canada"]},{"name":"Farncombe Family Digestive Health Research Institute, McMaster University , Hamilton, Ontario L8S 4K1 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4232-9141","authenticated-orcid":false,"given":"Yun Han","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, McMaster University , Hamilton, Ontario L8S 4K1 ,","place":["Canada"]},{"name":"Farncombe Family Digestive Health Research Institute, McMaster University , Hamilton, Ontario L8S 4K1 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Varun","family":"Dewan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, McMaster University , Hamilton, Ontario L8S 4K1 ,","place":["Canada"]},{"name":"Farncombe Family Digestive Health Research Institute, McMaster University , Hamilton, Ontario L8S 4K1 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7377-2835","authenticated-orcid":false,"given":"Fatemeh","family":"Vahedi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, McMaster University , Hamilton, Ontario L8S 4K1 ,","place":["Canada"]},{"name":"McMaster Immunology Research Centre, Michael G. DeGroote Institute for Infectious Disease Research, McMaster University , Hamilton, Ontario L8S 4K1 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saad","family":"Syed","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University , Hamilton, Ontario L8S 4K1 ,","place":["Canada"]},{"name":"Department of Medicine, McMaster University , Hamilton, Ontario L8S 4K1 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle E","family":"Fontes","sequence":"additional","affiliation":[{"name":"Farncombe Family Digestive Health Research Institute, McMaster University , Hamilton, Ontario L8S 4K1 ,","place":["Canada"]},{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University , Hamilton, Ontario L8S 4K1 ,","place":["Canada"]},{"name":"Department of Medicine, McMaster University , Hamilton, Ontario L8S 4K1 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1139-1468","authenticated-orcid":false,"given":"Ali A","family":"Ashkar","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, McMaster University , Hamilton, Ontario L8S 4K1 ,","place":["Canada"]},{"name":"McMaster Immunology Research Centre, Michael G. DeGroote Institute for Infectious Disease Research, McMaster University , Hamilton, Ontario L8S 4K1 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael G","family":"Surette","sequence":"additional","affiliation":[{"name":"Farncombe Family Digestive Health Research Institute, McMaster University , Hamilton, Ontario L8S 4K1 ,","place":["Canada"]},{"name":"McMaster Immunology Research Centre, Michael G. DeGroote Institute for Infectious Disease Research, McMaster University , Hamilton, Ontario L8S 4K1 ,","place":["Canada"]},{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University , Hamilton, Ontario L8S 4K1 ,","place":["Canada"]},{"name":"Department of Medicine, McMaster University , Hamilton, Ontario L8S 4K1 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waliul I","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, McMaster University , Hamilton, Ontario L8S 4K1 ,","place":["Canada"]},{"name":"Farncombe Family Digestive Health Research Institute, McMaster University , Hamilton, Ontario L8S 4K1 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,5,15]]},"reference":[{"key":"2025030417562181200_r1","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/S1471-4892(02)00215-1","article-title":"Neuroimmune and epithelial interactions in intestinal inflammation","volume":"2","author":"Sharkey","year":"2002","journal-title":"Curr. 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