title: Cord blood Streptococcus pneumoniae-specific cellular immune responses predict early pneumococcal carriage in high-risk infants in Papua New Guinea.
abstract: 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. 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. Significantly higher PspA-specific interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-5, IL-6, IL-10 and IL-13 responses, and lower dPly-IL-6 responses were produced in CBMC cultures of PNG compared to AUS newborns. Higher CBMC PspA-IL-5 and PspA-IL-13 responses correlated with a higher proportion of cord CD4 T cells, and higher dPly-IL-6 responses with a higher frequency of cord antigen-presenting cells. In the PNG cohort, higher PspA-specific IL-5 and IL-6 CBMC responses were associated independently and significantly with increased risk of earlier pneumococcal colonization, while a significant protective effect was found for higher PspA-IL-10 CBMC responses. 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.
authors.affiliation: Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea.
authors.forename: J P
authors.initials: JP
authors.lastname: Francis
authors.affiliation: School of Paediatrics and Child Health, University of Western Australia, Perth, Australia.
authors.forename: P C
authors.initials: PC
authors.lastname: Richmond
authors.affiliation: Telethon Kids Institute, University of Western Australia, Perth, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Strickland
authors.affiliation: School of Paediatrics and Child Health, University of Western Australia, Perth, Australia.
authors.forename: S L
authors.initials: SL
authors.lastname: Prescott
authors.affiliation: Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea.
authors.forename: W S
authors.initials: WS
authors.lastname: Pomat
authors.affiliation: Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea.
authors.forename: A
authors.initials: A
authors.lastname: Michael
authors.affiliation: Telethon Kids Institute, University of Western Australia, Perth, Australia.
authors.forename: M A
authors.initials: MA
authors.lastname: Nadal-Sims
authors.affiliation: Telethon Kids Institute, University of Western Australia, Perth, Australia.
authors.forename: C J
authors.initials: CJ
authors.lastname: Edwards-Devitt
authors.affiliation: Telethon Kids Institute, University of Western Australia, Perth, Australia.
authors.forename: P G
authors.initials: PG
authors.lastname: Holt
authors.affiliation: Telethon Kids Institute, University of Western Australia, Perth, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Lehmann
authors.affiliation: Telethon Kids Institute, University of Western Australia, Perth, Australia.
authors.forename: A H J
authors.initials: AH
authors.lastname: van den Biggelaar
mesh_terms: D000907:Antibodies, Bacterial / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D001315:Australia; D001426:Bacterial Proteins / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D005260:Female; D005312:Fetal Blood / Q000276:immunology* / Q000382:microbiology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007231:Infant, Newborn; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000382:microbiology; D010219:Papua New Guinea; D011008:Pneumococcal Infections / Q000276:immunology* / Q000382:microbiology; D011247:Pregnancy; D012306:Risk; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; C051592:pneumococcal surface protein A
keywords: Papua New Guinea; PspA; colonization; newborn; pneumococcal immunity