{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:53:25Z","timestamp":1790380405035,"version":"4.1.0"},"reference-count":54,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2014,9,9]],"date-time":"2014-09-09T00:00:00Z","timestamp":1410220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2014,10,31]],"date-time":"2014-10-31T00:00:00Z","timestamp":1414713600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2014,10,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Signal transduction via MyD88, an adaptor protein engaged by the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) family receptors, has a crucial role in host defenses against group B streptococcus (GBS). To examine the contribution of IL-1R signaling to MyD88-dependent host defenses, we analyzed GBS infection in type I IL-1R (IL-1RI)-deficient mice. Most of these animals displayed clinical signs of sepsis and neurological disease and died after a challenge with a bacterial dose that did not cause illness or death in any of the wild-type animals. Moreover, bacterial numbers in the blood and brains of the immunodefective mice were considerably increased. The ability of blood leukocytes or bone marrow-derived macrophages to kill GBS<jats:italic>in vitro<\/jats:italic>was not affected by a lack of IL-1RI. However, it was found in a newly developed model of GBS-induced peritoneal inflammation that IL-1 signaling selectively promoted the production of the chemokines KC and MIP-1\u03b1 and neutrophil recruitment. Moreover, the secretion of KC and MIP-1\u03b1, but not tumor necrosis factor alpha, by peritoneal macrophages stimulated with GBS was significantly decreased in the absence of IL-1RI. Accordingly, the number of neutrophils in the blood and the concentration of myeloperoxidase, a neutrophil marker, in infected organs were severely reduced in the immunodefective mice during GBS disease, concomitantly with a reduction in tissue KC and MIP-1\u03b1 levels. In conclusion, IL-1RI plays a crucial role in host defenses against GBS by inducing the high-level production of chemokines and the subsequent recruitment of neutrophilic polymorphonuclear leukocytes to infection sites.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>Group B streptococcus (GBS) is a serious and frequent human pathogen. Experimental infection with this bacterium has been widely used to understand the mechanism whereby the body\u2019s first line of defense, represented by cells and molecules of the innate immune system, fights infections. In both humans and mice, defective function of the adaptor molecule MyD88 has been associated with extreme susceptibility to infection by GBS and other extracellular bacteria. We show here that lack of signaling by interleukin-1 (IL-1) cytokines can largely, although not completely, explain the increased susceptibility to infection observed in the absence of MyD88 function. We show, in particular, that IL-1 signaling through the IL-1 receptor promotes the production of the leukocyte attractant chemokines KC and MIP-1\u03b1 and recruitment of neutrophils to GBS infection sites, thereby enabling these leukocytes to clear the infection. Our findings indicate that stimulation of IL-1 signaling may be useful as an alternative therapeutic strategy to treat GBS infections.<\/jats:p>","DOI":"10.1128\/mbio.01428-14","type":"journal-article","created":{"date-parts":[[2014,9,10]],"date-time":"2014-09-10T00:27:13Z","timestamp":1410308833000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":39,"title":["Essential Role of Interleukin-1 Signaling in Host Defenses Against Group B Streptococcus"],"prefix":"10.1128","volume":"5","author":[{"given":"Carmelo","family":"Biondo","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Mancuso","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelina","family":"Midiri","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Signorino","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Domina","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Lanza Cariccio","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Venza","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Sperimentali Medico-Chirurgiche Specialistiche ed Odontostomatologiche, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Venza","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Sperimentali Medico-Chirurgiche Specialistiche ed Odontostomatologiche, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Teti","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concetta","family":"Beninati","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)61651-6"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cir325"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/432804"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/599369"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.2217\/17460913.4.2.201"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2013.06.003"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.61.1.227-235.1993"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.5.1683-1687.1997"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.9.3731-3735.1997"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.5.3126"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075266"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.1.295-300.2004"},{"key":"e_1_3_3_14_2","first-page":"1506","article-title":"The role of endosomal Toll-like receptors in bacterial recognition","volume":"16","author":"Biondo C","year":"2012","unstructured":"BiondoC MancusoG BeninatiC IariaC RomeoO CascioA TetiG . 2012. 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