{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T11:57:07Z","timestamp":1791460627022,"version":"4.3.4"},"reference-count":58,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T00:00:00Z","timestamp":1585008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,4,28]],"date-time":"2020-04-28T00:00:00Z","timestamp":1588032000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100008908","name":"University of Messina","doi-asserted-by":"crossref","award":["FFABR2019"],"award-info":[{"award-number":["FFABR2019"]}],"id":[{"id":"10.13039\/501100008908","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008908","name":"University of Messina","doi-asserted-by":"crossref","award":["FFABR2018"],"award-info":[{"award-number":["FFABR2018"]}],"id":[{"id":"10.13039\/501100008908","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2020,4,28]]},"abstract":"<jats:p>The pneumococcus is a bacterium that frequently causes infections in the lungs, ears, sinus cavities, and meninges. During these infections, body defenses are triggered by tissue-resident cells that use specialized receptors, such as Toll-like receptors (TLRs), to sense the presence of bacteria. We show here that pneumococci are predominantly detected by TLRs that are located inside intracellular vacuoles, including endosomes, where these receptors can sense the presence of nucleic acids released from ingested bacteria. Mice that simultaneously lacked three of these receptors (specifically, TLR7, TLR9, and TLR13) were extremely susceptible to lung infection and rapidly died after inhalation of pneumococci. Moreover, tissue-resident macrophages from these mice were impaired in their ability to respond to the presence of pneumococci by producing inflammatory mediators capable of recruiting polymorphonuclear leucocytes to infection sites. This information may be useful to develop drugs to treat pneumococcal infections, particularly those caused by antibiotic-resistant strains.<\/jats:p>","DOI":"10.1128\/mbio.00415-20","type":"journal-article","created":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T12:54:46Z","timestamp":1585054486000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":31,"title":["Nucleic Acid-Sensing Toll-Like Receptors Play a Dominant Role in Innate Immune Recognition of Pneumococci"],"prefix":"10.1128","volume":"11","author":[{"given":"Agata","family":"Fam\u00e0","sequence":"first","affiliation":[{"name":"Department of Human Pathology, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelina","family":"Midiri","sequence":"additional","affiliation":[{"name":"Department of Human Pathology, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Mancuso","sequence":"additional","affiliation":[{"name":"Department of Human Pathology, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmelo","family":"Biondo","sequence":"additional","affiliation":[{"name":"Department of Human Pathology, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Germana","family":"Lentini","sequence":"additional","affiliation":[{"name":"Department of Human Pathology, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Galbo","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological and Pharmaceutical Sciences, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Miriam","family":"Giardina","sequence":"additional","affiliation":[{"name":"Department of Human Pathology, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe Valerio","family":"De Gaetano","sequence":"additional","affiliation":[{"name":"Department of Human Pathology, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Letizia","family":"Romeo","sequence":"additional","affiliation":[{"name":"Department of Human Pathology, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6315-8644","authenticated-orcid":false,"given":"Giuseppe","family":"Teti","sequence":"additional","affiliation":[{"name":"Charybdis Vaccines Srl, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concetta","family":"Beninati","sequence":"additional","affiliation":[{"name":"Department of Human Pathology, University of Messina, Messina, Italy"},{"name":"Scylla Biotech Srl, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a010215"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001432-200404000-00010"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2011.03603.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06246"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.2.595-601.1999"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.9.5240"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900688"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00001-11"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201242683"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2005.00578.x"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2015.128"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201644"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.02.015"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.24.021605.090552"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.5.3132"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-12-139"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2006-0166OC"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2007.04.003"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.1.298-307.2005"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2016.09.003"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1086\/342845"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1086\/591626"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2006.00814.x"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0435928100"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.10.6479-6487.2005"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001191"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.72.2.788-794.2004"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1006\/mpat.1997.0150"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00723"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2013.12.002"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3005"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3073"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2011.01746.x"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1158298"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00168-16"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.9.6246"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1615\/critrevimmunol.v26.i4.20"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.65.9.3731-3735.1997"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.5.3126"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01403-06"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2004.08.007"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201242532"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1733"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0607181103"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501014"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2448"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2010.189"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M802848200"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01209"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni0602-499"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01243"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1403173"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.02282-14"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1200898"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0160249"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0036588"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.10.6346"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01428-14"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.00415-20","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.00415-20","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T02:54:15Z","timestamp":1646708055000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mBio.00415-20"}},"subtitle":[],"editor":[{"given":"Alan","family":"Sher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,4,28]]},"references-count":58,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,4,28]]}},"alternative-id":["10.1128\/mBio.00415-20"],"URL":"https:\/\/doi.org\/10.1128\/mbio.00415-20","relation":{},"ISSN":["2161-2129","2150-7511"],"issn-type":[{"value":"2161-2129","type":"print"},{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,28]]},"assertion":[{"value":"2020-02-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00415-20"}}