{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T05:11:34Z","timestamp":1781241094267,"version":"3.54.1"},"reference-count":40,"publisher":"Informa UK Limited","issue":"6","license":[{"start":{"date-parts":[[2017,6,3]],"date-time":"2017-06-03T00:00:00Z","timestamp":1496448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":["www.tandfonline.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Enterococcus faecalis is a resident lactic acid bacterium in the human intestine. Its immunostimulatory action was reported to be enhanced by heat sterilization. To investigate its beneficial actions, we evaluated the ability of 10 E. faecalis strains to induce interleukin-12 (IL-12) production in a mouse macrophage cell line, J774.1 and found that the strain, E. faecalis IC-1, had a potent IL-12-inducing ability. Furthermore, we investigated the underlying mechanism by treating IC-1 cells with RNase or lysozyme. Its activity almost disappeared and an antagonist of Toll-like receptor (TLR) 7 inhibited this activity. Moreover, lysozyme-treated IC-1 bacteria were not phagocytized by J774.1 cells, and did not induce IL-12 production. Based on our results, we propose that macrophages recognize the cell wall components of IC-1, leading to phagocytosis. The IC-1 RNA is then recognized by TLR7, which induces the production of IL-12.<\/jats:p>","DOI":"10.1080\/09168451.2017.1295799","type":"journal-article","created":{"date-parts":[[2017,4,13]],"date-time":"2017-04-13T10:16:49Z","timestamp":1492078609000},"page":"1099-1105","update-policy":"https:\/\/doi.org\/10.1080\/tandf_crossmark_01","source":"Crossref","is-referenced-by-count":3,"title":["RNA and a cell wall component of <i>Enterococcus faecalis<\/i> IC-1 are required for phagocytosis and interleukin 12 production by the mouse macrophage cell line J774.1"],"prefix":"10.1080","volume":"81","author":[{"given":"Junpei","family":"Nakase","sequence":"first","affiliation":[{"name":"Central Research Institute, ITO EN, Ltd., Makinohara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuuichi","family":"Ukawa","sequence":"additional","affiliation":[{"name":"Central Research Institute, ITO EN, Ltd., Makinohara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syoji","family":"Takemoto","sequence":"additional","affiliation":[{"name":"Research & Development Division, Chichiyasu Company, Hatsukaichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayoshi","family":"Kubo","sequence":"additional","affiliation":[{"name":"Research & Development Division, Chichiyasu Company, Hatsukaichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko M","family":"Sagesaka","sequence":"additional","affiliation":[{"name":"Central Research Institute, ITO EN, Ltd., Makinohara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Aoki-Yoshida","sequence":"additional","affiliation":[{"name":"Department of Applied Biological Chemistry, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamoru","family":"Totsuka","sequence":"additional","affiliation":[{"name":"Department of Applied Biological Chemistry, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"301","published-online":{"date-parts":[[2017,6,3]]},"reference":[{"issue":"12","key":"2021040105202997900_CIT0001","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1038\/sj.ejcn.1600663","article-title":"The effect of consumption of milk fermented by Lactobacillus casei strain Shirota on the intestinal microflora and immune parameters in humans","volume":"52","author":"Spanhaak","year":"1998","journal-title":"Eur J Clin Nutr"},{"issue":"6","key":"2021040105202997900_CIT0002","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1007\/s12275-013-3279-2","article-title":"Lactobacillus paracasei subsp. paracasei LC01 positively modulates intestinal microflora in healthy young adults","volume":"51","author":"Zhang","year":"2013","journal-title":"J Microbiol"},{"issue":"9","key":"2021040105202997900_CIT0003","doi-asserted-by":"publisher","first-page":"1971","DOI":"10.1271\/bbb.90144","article-title":"Efficacy of oral administration of a heat-killed Lactobacillus gasseri OLL2809 on patients of Japanese cedar pollinosis with high Japanese-cedar pollen-specific IgE","volume":"73","author":"Gotoh","year":"2009","journal-title":"Biosci Biotechnol Biochem"},{"issue":"9","key":"2021040105202997900_CIT0004","doi-asserted-by":"publisher","first-page":"1652","DOI":"10.1271\/bbb.69.1652","article-title":"Effect of milk fermented with Lactobacillus acidophilus strain L-92 on symptoms of Japanese cedar pollen allergy: a randomized placebo-controlled trial","volume":"69","author":"Ishida","year":"2005","journal-title":"Biosci Biotechnol Biochem"},{"issue":"9","key":"2021040105202997900_CIT0005","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1111\/mim.2006.50.issue-9","article-title":"Preliminary human study for possible alteration of serum immunoglobulin E production in perennial allergic rhinitis with fermented milk prepared with Lactobacillus gasseri TMC0356","volume":"50","author":"Morita","year":"2006","journal-title":"Microbiol Immunol"},{"issue":"6","key":"2021040105202997900_CIT0006","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1038\/ejcn.2010.19","article-title":"Regulation of abdominal adiposity by probiotics (Lactobacillus gasseri SBT2055) in adults with obese tendencies in a randomized controlled trial","volume":"64","author":"Kadooka","year":"2010","journal-title":"Eur J Clin Nutr"},{"key":"2021040105202997900_CIT0007","doi-asserted-by":"publisher","first-page":"1640","DOI":"10.1186\/1475-2891-12-138","article-title":"Hypocaloric diet supplemented with probiotic cheese improves body mass index and blood pressure indices of obese hypertensive patients\u2013a randomized double-blind placebo-controlled pilot study","volume":"12","author":"Sharafedtinov","year":"2013","journal-title":"Nutr J"},{"issue":"4","key":"2021040105202997900_CIT0008","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1017\/S0022029909990173","article-title":"Effect of fermented milk containing Lactobacillus acidophilus and Bifidobacterium longum on plasma lipids of women with normal or moderately elevated cholesterol","volume":"76","author":"Andrade","year":"2009","journal-title":"J Dairy Res"},{"issue":"26","key":"2021040105202997900_CIT0009","doi-asserted-by":"publisher","first-page":"11080","DOI":"10.1021\/jf071786o","article-title":"Heat-killed cells of lactobacilli skew the immune response toward T helper 1 polarization in mouse splenocytes and dendritic cell-treated T cells","volume":"55","author":"Chuang","year":"2007","journal-title":"J Agric Food Chem"},{"issue":"2","key":"2021040105202997900_CIT0010","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1111\/j.1574-695X.2012.01003.x","article-title":"Immunomodulating and anti-infective effects of a novel strain of Lactobacillus paracasei that strongly induces interleukin-12","volume":"66","author":"Iwabuchi","year":"2012","journal-title":"FEMS Immunol Med Microbiol"},{"issue":"1","key":"2021040105202997900_CIT0011","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1111\/cei.2006.143.issue-1","article-title":"Natural killer cell activities of synbiotic Lactobacillus casei ssp. casei in conjunction with dextran","volume":"143","author":"Ogawa","year":"2006","journal-title":"Clin Exp Immunol"},{"issue":"1","key":"2021040105202997900_CIT0012","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1111\/cei.2006.146.issue-1","article-title":"Interleukin-12 is involved in the enhancement of human natural killer cell activity by Lactobacillus casei Shirota","volume":"146","author":"Takeda","year":"2006","journal-title":"Clin Exp Immunol"},{"issue":"9","key":"2021040105202997900_CIT0013","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1128\/CVI.00076-06","article-title":"Essential roles of monocytes in stimulating human peripheral blood mononuclear cells with Lactobacillus casei to produce cytokines and augment natural killer cell activity","volume":"13","author":"Shida","year":"2006","journal-title":"Clin Vaccine Immunol"},{"issue":"2","key":"2021040105202997900_CIT0014","first-page":"183","article-title":"Lactobacillus casei ssp. casei induced Th1 cytokine profile and natural killer cells activity in invasive ductal carcinoma bearing mice","volume":"11","author":"Soltan Dallal","year":"2012","journal-title":"Iran J Allergy Asthma Immunol"},{"issue":"5","key":"2021040105202997900_CIT0015","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/j.ypmed.2004.07.019","article-title":"Modulation of natural killer cell activity by supplementation of fermented milk containing Lactobacillus casei in habitual smokers","volume":"40","author":"Morimoto","year":"2005","journal-title":"Prev Med"},{"issue":"4","key":"2021040105202997900_CIT0016","doi-asserted-by":"crossref","DOI":"10.1007\/s11357-012-9434-6","article-title":"Oral supplementation with Lactobacillus delbrueckii subsp. bulgaricus 8481 enhances systemic immunity in elderly subjects","volume":"35","author":"Moro-Garc\u00eda","year":"2013","journal-title":"Age (Dordr)"},{"key":"2021040105202997900_CIT0017","doi-asserted-by":"crossref","first-page":"4638","DOI":"10.1038\/srep04638","article-title":"Oral administration of Lactobacillus gasseri SBT2055 is effective for preventing influenza in mice","volume":"4","author":"Nakayama","year":"2014","journal-title":"Sci Rep"},{"issue":"12","key":"2021040105202997900_CIT0018","doi-asserted-by":"publisher","first-page":"2246","DOI":"10.1016\/j.intimp.2011.09.012","article-title":"Effects of oral administration of yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 and its exopolysaccharides against influenza virus infection in mice","volume":"11","author":"Nagai","year":"2011","journal-title":"Int Immunopharmacol"},{"issue":"2","key":"2021040105202997900_CIT0019","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1111\/fim.2012.64.issue-2","article-title":"Heat-killed Lactobacillus gasseri TMC0356 protects mice against influenza virus infection by stimulating gut and respiratory immune responses","volume":"64","author":"Kawase","year":"2012","journal-title":"FEMS Immunol Med Microbiol"},{"issue":"5","key":"2021040105202997900_CIT0020","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1271\/bbb.90749","article-title":"Effects of Bifidobacterium longum BB536 administration on influenza infection, influenza vaccine antibody titer, and cell-mediated immunity in the elderly","volume":"74","author":"Namba","year":"2010","journal-title":"Biosci Biotechnol Biochem"},{"issue":"7","key":"2021040105202997900_CIT0021","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1017\/S000711451000173X","article-title":"Reducing the risk of infection in the elderly by dietary intake of yoghurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1","volume":"104","author":"Makino","year":"2010","journal-title":"Br J Nutr"},{"issue":"6","key":"2021040105202997900_CIT0022","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1111\/lam.2014.59.issue-6","article-title":"Effects of probiotic Lactobacillus brevis KB290 on incidence of influenza infection among schoolchildren: an open-label pilot study","volume":"59","author":"Waki","year":"2014","journal-title":"Lett Appl Microbiol"},{"issue":"10","key":"2021040105202997900_CIT0023","doi-asserted-by":"publisher","first-page":"1856","DOI":"10.1017\/S0007114512003753","article-title":"Immunoprotective effects of oral intake of heat-killed Lactobacillus pentosus strain b240 in elderly adults: a randomised, double-blind, placebo-controlled trial","volume":"109","author":"Shinkai","year":"2013","journal-title":"Br J Nutr"},{"issue":"3","key":"2021040105202997900_CIT0024","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1111\/cmi.2005.7.issue-3","article-title":"Strong immunostimulation in murine immune cells by Lactobacillus rhamnosus GG DNA containing novel oligodeoxynucleotide pattern","volume":"7","author":"Iliev","year":"2005","journal-title":"Cell Microbiol"},{"issue":"9","key":"2021040105202997900_CIT0025","doi-asserted-by":"publisher","first-page":"3306","DOI":"10.3168\/jds.S0022-0302(06)72367-0","article-title":"Induction of interleukin-12 by lactobacillus strains having a rigid cell wall resistant to intracellular digestion","volume":"89","author":"Shida","year":"2006","journal-title":"J Dairy Sci"},{"issue":"3","key":"2021040105202997900_CIT0026","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1111\/j.1348-0421.2009.00189.x","article-title":"Lipoteichoic acids on Lactobacillus plantarum cell surfaces correlate with induction of interleukin-12p40 production","volume":"54","author":"Hirose","year":"2010","journal-title":"Microbiol Immunol"},{"issue":"8","key":"2021040105202997900_CIT0027","doi-asserted-by":"publisher","first-page":"2873","DOI":"10.3168\/jds.S0022-0302(06)72560-7","article-title":"Immunomodulatory effects of polysaccharides produced by Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1","volume":"89","author":"Makino","year":"2006","journal-title":"J Dairy Sci"},{"issue":"5","key":"2021040105202997900_CIT0028","doi-asserted-by":"publisher","first-page":"M260","DOI":"10.1111\/j.1750-3841.2011.02161.x","article-title":"Heat-killed lactic acid bacteria enhance immunomodulatory potential by skewing the immune response toward Th1 polarization","volume":"76","author":"Ou","year":"2011","journal-title":"J Food Sci"},{"key":"2021040105202997900_CIT0029","first-page":"17","article-title":"Effect of various preparation types of the Enterococcus faecalis FK-23 strain on the ability of eliciting tumor necrosis factor from macrophages isolated from mice","volume":"21","author":"Shimada","year":"2003","journal-title":"Med J Jpn Red Cross Soc Wakayama Med Center"},{"issue":"4","key":"2021040105202997900_CIT0030","first-page":"188","article-title":"Effect of the consumption of heat-killed Enterococcus faecalis EC-12 preparation on microbiota and metabolic activity of the feces in healthy adults","volume":"16","author":"Terada","year":"2001","journal-title":"Microb Ecol Health Dis"},{"issue":"2","key":"2021040105202997900_CIT0031","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1080\/08910600510044507","article-title":"Effect of a cell preparation of Enterococcus faecalis strain EC-12 on digesta flow and recovery from constipation in a pig model and human subjects","volume":"17","author":"Tsukahara","year":"2005","journal-title":"Microb Ecol Health Dis"},{"issue":"2","key":"2021040105202997900_CIT0032","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/0922-338X(96)85030-6","article-title":"Identification of an RNA fraction from Enterococcus faecalis FK-23 cells as the antihypertensive compound","volume":"82","author":"Shimada","year":"1996","journal-title":"J Ferment Bioeng"},{"issue":"1","key":"2021040105202997900_CIT0033","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1111\/j.1574-695X.2010.00752.x","article-title":"Nucleic acids of Enterococcus faecalis strain EC-12 are potent Toll-like receptor 7 and 9 ligands inducing interleukin-12 production from murine splenocytes and murine macrophage cell line J774.1","volume":"61","author":"Inoue","year":"2011","journal-title":"FEMS Immunol Med Microbiol"},{"issue":"8","key":"2021040105202997900_CIT0034","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1084\/jem.20050914","article-title":"Nucleic acids of mammalian origin can act as endogenous ligands for Toll-like receptors and may promote systemic lupus erythematosus","volume":"202","author":"Barrat","year":"2005","journal-title":"J Exp Med"},{"issue":"44","key":"2021040105202997900_CIT0035","doi-asserted-by":"publisher","first-page":"37107","DOI":"10.1074\/jbc.M504951200","article-title":"TLR3 and TLR7 are targeted to the same intracellular compartments by distinct regulatory elements","volume":"280","author":"Nishiya","year":"2005","journal-title":"J Biol Chem"},{"key":"2021040105202997900_CIT0036","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1146\/annurev.iy.13.040195.001343","article-title":"Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity","volume":"13","author":"Trinchieri","year":"1995","journal-title":"Annu Rev Immunol"},{"issue":"6603","key":"2021040105202997900_CIT0037","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1038\/383787a0","article-title":"Functional diversity of helper T lymphocytes","volume":"383","author":"Abbas","year":"1996","journal-title":"Nature"},{"issue":"6","key":"2021040105202997900_CIT0038","doi-asserted-by":"publisher","first-page":"e0129806","DOI":"10.1371\/journal.pone.0129806","article-title":"RNA of Enterococcus faecalis strain EC-12 Is a major component inducing interleukin-12 production from human monocytic cells","volume":"10","author":"Nishibayashi","year":"2015","journal-title":"PLoS ONE"},{"issue":"4","key":"2021040105202997900_CIT0039","doi-asserted-by":"publisher","first-page":"e32588","DOI":"10.1371\/journal.pone.0032588","article-title":"Spherical lactic acid bacteria activate plasmacytoid dendritic cells immunomodulatory function via TLR9-dependent crosstalk with myeloid dendritic cells","volume":"7","author":"Jounai","year":"2012","journal-title":"PLoS ONE"},{"issue":"1","key":"2021040105202997900_CIT0040","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1084\/jem.20031237","article-title":"Toll-like receptors induce a phagocytic gene program through p38","volume":"199","author":"Doyle","year":"2004","journal-title":"J Exp Med"}],"container-title":["Bioscience, Biotechnology, and Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/bbb\/article-pdf\/81\/6\/1099\/36845587\/bbb1099.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/bbb\/article-pdf\/81\/6\/1099\/36845587\/bbb1099.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T11:51:59Z","timestamp":1654602719000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bbb\/article\/81\/6\/1099\/5938080"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,3]]},"references-count":40,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2017,6,3]]},"published-print":{"date-parts":[[2017,6,3]]}},"URL":"https:\/\/doi.org\/10.1080\/09168451.2017.1295799","relation":{},"ISSN":["0916-8451","1347-6947"],"issn-type":[{"value":"0916-8451","type":"print"},{"value":"1347-6947","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2017,6,3]]},"published":{"date-parts":[[2017,6,3]]},"assertion":[{"value":"The publishing and review policy for this title is described in its Aims & Scope.","order":1,"name":"peerreview_statement","label":"Peer Review Statement"},{"value":"http:\/\/www.tandfonline.com\/action\/journalInformation?show=aimsScope&journalCode=tbbb20","URL":"http:\/\/www.tandfonline.com\/action\/journalInformation?show=aimsScope&journalCode=tbbb20","order":2,"name":"aims_and_scope_url","label":"Aim & Scope"},{"value":"2016-10-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-01-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-04-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}