Abstract
Respiratory infection caused by Streptococcus pneumoniae is a leading cause of morbidity and mortality in older adults. Acquired CD4+ T cell mechanism are essential for the protection against colonization and subsequent development of infections by S. pneumoniae. In this study, we hypothesized that age-related changes within the CD4+ T-cell population compromise CD4+ T-cell specific responses to S. pneumoniae, thereby contributing to increased susceptibility at older age. To this end, we interrogated the CD4+ T-cell response against the immunogenic pneumococcal protein AliB, part of the unique oligopeptide ABC transporter system responsible for the uptake of nutrients for the bacterium and crucial for the development of pneumococcal meningitis, in healthy young and older adults. Specifically, proliferation of CD4+ T cells as well as concomitant cytokine profiles and phenotypic markers implied in immunosenescence were studied. Older adults showed decreased AliB-induced CD4+ T-cell proliferation that is associated with an increased frequency of regulatory T cells and lower levels of active CD25+CD127+CTLA-4−TIGIT-CD4+T cells. Additionally, levels of pro-inflammatory cytokines IFNy and IL-17F were decreased at older age. Our findings indicate that key features of a pneumococcal-specific CD4+ T-cell immune response are altered at older age, which may contribute to enhanced susceptibility for pneumococcal infections.
Highlights
Streptococcus pneumoniae is a leading cause of respiratory infections in adults above 65 years of age, which is associated with substantial morbidity and mortality (Vila-Corcoles and Ochoa-Gondar, 2013; Drijkoningen and Rohde, 2014)
To explore whether human anti-pneumococcal CD4+ T cell immunity is negatively impacted at older age, we examined the presence of these immunosenescent features on CD4+ T cells of young and older adults using an important class of pneumococcal proteins
Adults above 65 years of age become increasingly susceptible to pneumococcal infections associated with substantial morbidity and mortality
Summary
Streptococcus pneumoniae is a leading cause of respiratory infections in adults above 65 years of age, which is associated with substantial morbidity and mortality (Vila-Corcoles and Ochoa-Gondar, 2013; Drijkoningen and Rohde, 2014). The induced effector CD4+ T-cell response is modulated by pneumococcal-specific regulatory T cells (Tregs) to prevent excessive tissue damage and subsequent severe infection due to compromised tissue integrity and barriers (Pido-Lopez et al, 2011; Neill et al, 2012). Both low CD4+ T-cell effector responses and increased numbers of Tregs are associated with positive pneumococcal carriage in children and young adults (Zhang et al, 2007; Zhang et al, 2011; Jiang et al, 2015; Mubarak et al, 2016), highlighting the importance of these responses in regulating colonization, a pre-requisite towards disease. Less is known about alterations in pneumococcal-specific CD4+ T cell immunity at older age
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