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Protective Contributions against Invasive Streptococcus pneumoniae Pneumonia of Antibody and Th17-Cell Responses to Nasopharyngeal Colonisation

Cohen, JM; Khandavilli, S; Camberlein, E; Hyams, C; Baxendale, HE; Brown, JS; (2011) Protective Contributions against Invasive Streptococcus pneumoniae Pneumonia of Antibody and Th17-Cell Responses to Nasopharyngeal Colonisation. PLOS ONE , 6 (10) , Article e25558. 10.1371/journal.pone.0025558. Green open access

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Abstract

The nasopharyngeal commensal bacteria Streptococcus pneumoniae is also a frequent cause of serious infections. Nasopharyngeal colonisation with S. pneumoniae inhibits subsequent re-colonisation by inducing Th17-cell adaptive responses, whereas vaccination prevents invasive infections by inducing antibodies to S. pneumoniae capsular polysaccharides. In contrast, protection against invasive infection after nasopharyngeal colonisation with mutant S. pneumoniae strains was associated with antibody responses to protein antigens. The role of colonisation-induced Th17-cell responses during subsequent invasive infections is unknown. Using mouse models, we show that previous colonisation with S. pneumoniae protects against subsequent lethal pneumonia mainly by preventing bacteraemia with a more modest effect on local control of infection within the lung. Previous colonisation resulted in CD4-dependent increased levels of Th17-cell cytokines during subsequent infectious challenge. However, mice depleted of CD4 cells prior to challenge remained protected against bacteraemia, whereas no protection was seen in antibody deficient mice and similar protection could be achieved through passive transfer of serum. Serum from colonised mice but not antibody deficient mice promoted phagocytosis of S. pneumoniae, and previously colonised mice were able to rapidly clear S. pneumoniae from the blood after intravenous inoculation. Thus, despite priming for a Th17-cell response during subsequent infection, the protective effects of prior colonisation in this model was not dependent on CD4 cells but on rapid clearance of bacteria from the blood by antibody-mediated phagocytosis. These data suggest that whilst nasopharyngeal colonisation induces a range of immune responses, the effective protective responses depend upon the site of subsequent infection.

Type: Article
Title: Protective Contributions against Invasive Streptococcus pneumoniae Pneumonia of Antibody and Th17-Cell Responses to Nasopharyngeal Colonisation
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0025558
Publisher version: http://dx.doi.org/10.1371/journal.pone.0025558
Language: English
Additional information: © 2011 Cohen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was undertaken at University College London Hospitals and University College London (UCL) which received a proportion of funding from the Department of Health's National Institute for Health Research Biomedical Research Centre's funding scheme. JMC was supported by a Clinical Research Training Fellowship from the Medical Research Council (G0700829). EC was supported by the Medical Research Council (grant G0600410). CH was supported by the Astor Foundation and with an unrestricted educational grant from GlaxoSmithKline towards the UCL MBPhD program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: INDEPENDENT ACQUIRED-IMMUNITY, PNEUMOCOCCAL DISEASE, T-CELLS, ABC TRANSPORTER, MICE, ESTABLISHMENT, PHAGOCYTOSIS, VACCINATION, INFECTION, VIRULENCE
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Internal Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1325601
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