The ontogeny of innate immunity in Gambian infants

Background: Neonatal infections are a major cause of childhood morbidity and mortality world-wide. Our limited understanding of how the neonatal immune system functions is one of the major roadblocks to the prevention and treatment of these infections. Pattern recognition receptors (PRRs) detect common microbial antigens and are critical in the early innate immune response. Mucosal exposure to bacterial antigen may shape the ontogeny of infant immunity. Methods: Longitudinal cohort study of healthy Gambian infants assessed at 6 time-points over the first year of life. Microbiological culture techniques were performed to detect bacteria colonising the nasopharynx. Secreted cytokine and antimicrobial protein (AMP) levels were measured in supernatants from in vitro whole blood assays testing responses to PRR agonists. Quantitative real-time polymerase chain reaction was used to measure PRR agonist induced transcriptional responses in whole blood. Results: 54 eligible infants were recruited at birth and 46 were followed-up until 12- months old. Bacterial colonisation of the nasopharyngeal mucosa occurred early in life. Infant age and bacterial colonisation status were significantly associated with the magnitude of specific PRR agonist induced intracellular immune pathway gene transcription and extracellular innate immune protein secretion. Co-stimulation of infant blood with NLR and TLR agonists induced synergistic effects on innate immune responses. Conclusions: Innate immune responses in Gambian infants are age-dependent and are associated with specific nasopharyngeal bacterial colonisation particularly during the neonatal period.Open Acces