{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T14:12:38Z","timestamp":1789913558423,"version":"4.0.1"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2016,5,1]],"date-time":"2016-05-01T00:00:00Z","timestamp":1462060800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI114800"],"award-info":[{"award-number":["R01AI114800"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["13IRG14560023"],"award-info":[{"award-number":["13IRG14560023"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:named-content content-type=\"genus-species\">Streptococcus pneumoniae<\/jats:named-content>\n                    (the pneumococcus) is capable of invading the heart. Herein we observed that pneumococcal invasion of the myocardium occurred soon after development of bacteremia and was continuous thereafter. Using immunofluorescence microscopy (IFM), we observed that\n                    <jats:named-content content-type=\"genus-species\">S. pneumoniae<\/jats:named-content>\n                    replication within the heart preceded visual signs of tissue damage in cardiac tissue sections stained with hematoxylin and eosin. Different\n                    <jats:named-content content-type=\"genus-species\">S. pneumoniae<\/jats:named-content>\n                    strains caused distinct cardiac pathologies: strain TIGR4, a serotype 4 isolate, caused discrete pneumococcus-filled microscopic lesions (microlesions), whereas strain D39, a serotype 2 isolate, was, in most instances, detectable only using IFM and was associated with foci of cardiomyocyte hydropic degeneration and immune cell infiltration. Both strains efficiently invaded the myocardium, but cardiac damage was entirely dependent on the pore-forming toxin pneumolysin only for D39. Early microlesions caused by TIGR4 and microlesions formed by a TIGR4 pneumolysin-deficient mutant were infiltrated with CD11b\n                    <jats:sup>+<\/jats:sup>\n                    and Ly6G-positive neutrophils and CD11b\n                    <jats:sup>+<\/jats:sup>\n                    and F4\/80-positive (F4\/80\n                    <jats:sup>+<\/jats:sup>\n                    ) macrophages. We subsequently demonstrated that macrophages in TIGR4-infected hearts died as a result of pneumolysin-induced necroptosis. The effector of necroptosis, phosphorylated mixed-lineage kinase domain-like protein (MLKL), was detected in CD11b\n                    <jats:sup>+<\/jats:sup>\n                    and F4\/80\n                    <jats:sup>+<\/jats:sup>\n                    cells associated with microlesions. Likewise, treatment of infected mice and THP-1 macrophages\n                    <jats:italic>in vitro<\/jats:italic>\n                    with the receptor-interacting protein 1 kinase (RIP1) inhibitor necrostatin-5 promoted the formation of purulent microlesions and blocked cell death, respectively. We conclude that pneumococci that have invaded the myocardium are an important cause of cardiac damage, pneumolysin contributes to cardiac damage in a bacterial strain-specific manner, and pneumolysin kills infiltrated macrophages via necroptosis, which alters the immune response.\n                  <\/jats:p>","DOI":"10.1128\/iai.00007-16","type":"journal-article","created":{"date-parts":[[2016,2,29]],"date-time":"2016-02-29T22:34:22Z","timestamp":1456785262000},"page":"1457-1469","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":64,"title":["Infiltrated Macrophages Die of Pneumolysin-Mediated Necroptosis following Pneumococcal Myocardial Invasion"],"prefix":"10.1128","volume":"84","author":[{"given":"Ryan P.","family":"Gilley","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norberto","family":"Gonz\u00e1lez-Juarbe","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"},{"name":"Department of Microbiology, The University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anukul T.","family":"Shenoy","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"},{"name":"Department of Microbiology, The University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis F.","family":"Reyes","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"},{"name":"Division of Pulmonary Diseases &amp; Critical Care Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter H.","family":"Dube","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos I.","family":"Restrepo","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Diseases &amp; Critical Care Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"},{"name":"Division of Pulmonary Diseases &amp; Critical Care Medicine, South Texas Veterans Health Care System, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos J.","family":"Orihuela","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"},{"name":"Department of Microbiology, The University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","first-page":"1","article-title":"Deaths: preliminary data for 2009","volume":"59","author":"Kochanek KD","year":"2011","unstructured":"Kochanek KD, Xu J, Murphy SL, Minino AM, Kung HC. 2011. 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