title: PcpA Promotes Higher Levels of Infection and Modulates Recruitment of Myeloid-Derived Suppressor Cells during Pneumococcal Pneumonia.
abstract: 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.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294;
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Walker
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294;
authors.forename: Lea
authors.identifier: http://orcid.org/0000-0002-1072-6599
authors.initials: L
authors.lastname: Novak
authors.affiliation: Department of Pediatrics, University of South Carolina School of Medicine, Columbia, SC 29203;
authors.forename: Rebecca
authors.initials: R
authors.lastname: Widener
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294;
authors.forename: James Aaron
authors.identifier: http://orcid.org/0000-0001-8111-4648
authors.initials: JA
authors.lastname: Grubbs
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294;
authors.forename: Janice
authors.initials: J
authors.lastname: King
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294;
authors.forename: Joanetha Y
authors.identifier: http://orcid.org/0000-0002-4153-7459
authors.initials: JY
authors.lastname: Hale
authors.affiliation: Sanofi Pasteur, Non-Clinical Product Performance, 69280 Marcy L'Etoile, France;
authors.forename: Martina M
authors.initials: MM
authors.lastname: Ochs
authors.affiliation: Sanofi Pasteur, Non-Clinical Product Performance, 69280 Marcy L'Etoile, France;
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Myers
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294; Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294; Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35294; and.
authors.forename: David E
authors.initials: DE
authors.lastname: Briles
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294; Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL 35294 treena@uab.edu.
authors.forename: Jessy
authors.identifier: http://orcid.org/0000-0002-6761-5662
authors.initials: J
authors.lastname: Deshane
mesh_terms: D000818:Animals; D016470:Bacteremia; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D056747:Immunomodulation; D018836:Inflammation Mediators / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000382:microbiology* / Q000401:mortality / Q000473:pathology; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D013997:Time Factors
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D016207:Cytokines; D018836:Inflammation Mediators; D047908:Intracellular Signaling Peptides and Proteins; C113653:PcpA protein, Streptococcus; D053221:TNF-Related Apoptosis-Inducing Ligand
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