Cord blood Streptococcus pneumoniae specific cellular immune responses predict early pneumococcal carriage in high-risk infants in Papua New Guinea.

Background In areas where Streptococcus pneumoniae is highly endemic, infants experience very early pneumococcal colonization of the upper respiratory tract with carriage often persisting into adulthood. We aimed to explore whether newborns in high risk areas have pre-existing pneumococcal-specific cellular immune responses that may affect early pneumococcal acquisition. Methods Cord blood mononuclear cells (CBMC) of 84 Papua New Guinean (PNG; high endemic) and 33 Australian (AUS; low endemic) newborns were stimulated in vitro with detoxified pneumolysin (dPly) or pneumococcal surface protein A (PspA; families 1 and 2) and compared for cytokine responses. Within the PNG cohort, associations between CBMC dPly and PspA-induced responses and pneumococcal colonization within the first month of life were studied. Results Significantly higher PspA-specific IFN-γ, TNF-α, IL-5, IL-6, IL-10 and IL-13 responses, and lower dPly-IL6 responses were produced in CBMC cultures of PNG compared to AUS newborns. Higher CBMC PspA-IL5 and PspA-IL13 responses were correlated with a higher proportion of CD4 T-cells in CBMC, and higher dPly-IL6 responses with a higher frequency of antigen presenting cells. In the PNG cohort, higher PspA-specific IL-5 and IL-6 CBMC responses were independently and significantly associated with increased risk of earlier pneumococcal colonization, while a significant protective effect was found for higher cord blood PspA-IL10 responses. Conclusions Pneumococcus-specific cellular immune responses differ between children born in pneumococcal high versus low endemic settings, which may contribute to the higher risk of infants in high endemic settings for early pneumococcal colonization, and hence disease. This article is protected by copyright. All rights reserved.