{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T22:37:22Z","timestamp":1778884642031,"version":"3.51.4"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"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":[[2016,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We used two different infection models to investigate the kinetics of the PcpA-dependent pneumococcal disease in mice. In a bacteremic pneumonia model, we observed a PcpA-dependent increase in bacterial burden in the lungs, blood, liver, bronchoalveolar lavage, and spleens of mice at 24 h postinfection. This PcpA-dependent effect on bacterial burden appeared earlier (within 12 h) in the focal pneumonia model, which lacks bacteremia or sepsis. Histological changes show that the ability of pneumococci to make PcpA was associated with unresolved inflammation in both models of infection. Using our bacteremic pneumonia model we further investigated the effects of PcpA on recruitment of innate immune regulatory cells. The presence of PcpA was associated with increased IL-6 levels, suppressed production of TRAIL, and reduced infiltration of polymorphonuclear cells. The ability of pneumococci to make PcpA negatively modulated both the infiltration and apoptosis of macrophages and the recruitment of myeloid-derived suppressor-like cells. The latter have been shown to facilitate the clearance and control of bacterial pneumonia. Taken together, the ability to make PcpA was strongly associated with increased bacterial burden, inflammation, and negative regulation of innate immune cell recruitment to the lung tissue during bacteremic pneumonia.<\/jats:p>","DOI":"10.4049\/jimmunol.1402518","type":"journal-article","created":{"date-parts":[[2016,2,2]],"date-time":"2016-02-02T03:43:39Z","timestamp":1454384619000},"page":"2239-2248","source":"Crossref","is-referenced-by-count":12,"title":["PcpA Promotes Higher Levels of Infection and Modulates Recruitment of Myeloid-Derived Suppressor Cells during Pneumococcal Pneumonia"],"prefix":"10.1093","volume":"196","author":[{"given":"Melissa M","family":"Walker","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1072-6599","authenticated-orcid":false,"given":"Lea","family":"Novak","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Widener","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of South Carolina School of Medicine , Columbia, SC 29203"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8111-4648","authenticated-orcid":false,"given":"James Aaron","family":"Grubbs","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janice","family":"King","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4153-7459","authenticated-orcid":false,"given":"Joanetha Y","family":"Hale","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina M","family":"Ochs","sequence":"additional","affiliation":[{"name":"Sanofi Pasteur, Non-Clinical Product Performance , 69280 Marcy L\u2019Etoile ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa E","family":"Myers","sequence":"additional","affiliation":[{"name":"Sanofi Pasteur, Non-Clinical Product Performance , 69280 Marcy L\u2019Etoile ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David E","family":"Briles","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham , Birmingham, AL 35294"},{"name":"Department of Genetics, University of Alabama at Birmingham , Birmingham, AL 35294"},{"name":"Department of Pediatrics, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6761-5662","authenticated-orcid":false,"given":"Jessy","family":"Deshane","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham , Birmingham, AL 35294"},{"name":"Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,3,1]]},"reference":[{"key":"2025030702141115600_r1","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/S0140-6736(09)61204-6","article-title":"Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates","volume":"374","author":"O\u2019Brien","year":"2009","journal-title":"Lancet"},{"key":"2025030702141115600_r2","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1016\/S0140-6736(04)16357-5","article-title":"Colonisation by Streptococcus pneumoniae and Staphylococcus aureus in healthy children","volume":"363","author":"Bogaert","year":"2004","journal-title":"Lancet"},{"key":"2025030702141115600_r3","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/nrmicro771","article-title":"The pathogenesis of streptococcal infections: from tooth decay to meningitis","volume":"1","author":"Mitchell","year":"2003","journal-title":"Nat. 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