期刊论文详细信息
PLoS Pathogens
Experimental Human Pneumococcal Carriage Augments IL-17A-dependent T-cell Defence of the Lung
Stephen B. Gordon1  Andrea M. Collins2  Mathieu Bangert3  Daniela M. Ferreira4  Angela D. Wright4  Adam K. A. Wright4  Jenna F. Gritzfeld4  Kondwani C. Jambo4 
[1] Comprehensive Local Research Network, Royal Liverpool and Broadgreen University Hospital Trust, Liverpool, United Kingdom;Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Chichiri, Blantyre, Malawi;National Institute for Health Research Biomedical Research Centre in Microbial Diseases, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, United Kingdom;Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
关键词: T cells;    Memory T cells;    Alveolar macrophages;    Blood;    Pneumonia;    Flow cytometry;    Pneumococcus;    Neutrophils;   
DOI  :  10.1371/journal.ppat.1003274
学科分类:生物科学(综合)
来源: Public Library of Science
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【 摘 要 】

Pneumococcal carriage is both immunising and a pre-requisite for mucosal and systemic disease. Murine models of pneumococcal colonisation show that IL-17A-secreting CD4+ T-cells (Th-17 cells) are essential for clearance of pneumococci from the nasopharynx. Pneumococcal-responding IL-17A-secreting CD4+ T-cells have not been described in the adult human lung and it is unknown whether they can be elicited by carriage and protect the lung from pneumococcal infection. We investigated the direct effect of experimental human pneumococcal nasal carriage (EHPC) on the frequency and phenotype of cognate CD4+ T-cells in broncho-alveolar lavage and blood using multi-parameter flow cytometry. We then examined whether they could augment ex vivo alveolar macrophage killing of pneumococci using an in vitro assay. We showed that human pneumococcal carriage leads to a 17.4-fold (p = 0.007) and 8-fold (p = 0.003) increase in the frequency of cognate IL-17A+ CD4+ T-cells in BAL and blood, respectively. The phenotype with the largest proportion were TNF+/IL-17A+ co-producing CD4+ memory T-cells (p<0.01); IFNγ+ CD4+ memory T-cells were not significantly increased following carriage. Pneumococci could stimulate large amounts of IL-17A protein from BAL cells in the absence of carriage but in the presence of cognate CD4+ memory T-cells, IL-17A protein levels were increased by a further 50%. Further to this we then show that alveolar macrophages, which express IL-17A receptors A and C, showed enhanced killing of opsonised pneumococci when stimulated with rhIL-17A (p = 0.013). Killing negatively correlated with RC (r = −0.9, p = 0.017) but not RA expression. We conclude that human pneumococcal carriage can increase the proportion of lung IL-17A-secreting CD4+ memory T-cells that may enhance innate cellular immunity against pathogenic challenge. These pathways may be utilised to enhance vaccine efficacy to protect the lung against pneumonia.

【 授权许可】

CC BY   

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