TY - JOUR
T1 - Neonatal innate cytokine responses to BCG controlling T-cell development vary between populations
AU - Van Den Biggelaar, Anita
AU - Prescott, Susan
AU - Roponen, M.
AU - Nadal-Sims, M.A.
AU - Devitt, C.J.
AU - Phuanukoonnon, S.
AU - Pomat, W.
AU - Tulic, Meri
AU - Lehmann, Deborah
AU - Siba, P.M.
AU - Richmond, Peter
AU - Holt, Patrick
PY - 2009
Y1 - 2009
N2 - Background: The protective effect of Mycobacterium bovis BCG vaccination against infection and atopy varies between populations. Objective: To identify differences in neonatal responses to BCG between diverse populations and study longitudinal associations with memory T-cell responses. Methods: Cord blood mononuclear cells were collected from Papua New Guinean (PNG) and Western Australian (WA) newborns. Toll-like receptor (TLR)-2, TLR4, and TLR9 mRNA expression and in vitro BCG-stimulated (±IFN-γ priming) innate cytokine responses were compared. When PNG infants were 3 months old, PBMCs were stimulated in vitro with Mycobacterium-purified protein derivative (PPD) to determine memory T-cell responses. Results: BCG-induced IL-10 and IFN-γ responses were significantly higher in cord blood mononuclear cells of PNG newborns, and TLR2 and TLR9 expression was significantly higher and TLR4 expression lower compared with WA newborns. High neonatal IL-10 and low IFN-γ responses to BCG were found to promote the development of PPD-memory TH2 responses in infancy, whereas neonatal BCG-TNFα responses inhibited the development of PPD-IL 10 responses. When primed with IFN-γ, BCG-induced TNF-α, IL-12p70, and in particular IFN-γ responses were enhanced to a significantly higher extent in WA than in PNG newborns. In response to IFN-γ priming and BCG stimulation, natural killer cells of WA newborns produced IFN-γ, whereas natural killer cells of PNG newborns contributed only indirectly to this response. Conclusion: Neonatal BCG-related innate immune responses control the differentiation of TH memory responses and vary between populations. This may explain differences in the effects of BCG vaccination between populations.
AB - Background: The protective effect of Mycobacterium bovis BCG vaccination against infection and atopy varies between populations. Objective: To identify differences in neonatal responses to BCG between diverse populations and study longitudinal associations with memory T-cell responses. Methods: Cord blood mononuclear cells were collected from Papua New Guinean (PNG) and Western Australian (WA) newborns. Toll-like receptor (TLR)-2, TLR4, and TLR9 mRNA expression and in vitro BCG-stimulated (±IFN-γ priming) innate cytokine responses were compared. When PNG infants were 3 months old, PBMCs were stimulated in vitro with Mycobacterium-purified protein derivative (PPD) to determine memory T-cell responses. Results: BCG-induced IL-10 and IFN-γ responses were significantly higher in cord blood mononuclear cells of PNG newborns, and TLR2 and TLR9 expression was significantly higher and TLR4 expression lower compared with WA newborns. High neonatal IL-10 and low IFN-γ responses to BCG were found to promote the development of PPD-memory TH2 responses in infancy, whereas neonatal BCG-TNFα responses inhibited the development of PPD-IL 10 responses. When primed with IFN-γ, BCG-induced TNF-α, IL-12p70, and in particular IFN-γ responses were enhanced to a significantly higher extent in WA than in PNG newborns. In response to IFN-γ priming and BCG stimulation, natural killer cells of WA newborns produced IFN-γ, whereas natural killer cells of PNG newborns contributed only indirectly to this response. Conclusion: Neonatal BCG-related innate immune responses control the differentiation of TH memory responses and vary between populations. This may explain differences in the effects of BCG vaccination between populations.
U2 - 10.1016/j.jaci.2009.03.040
DO - 10.1016/j.jaci.2009.03.040
M3 - Article
C2 - 19500827
VL - 124
SP - 544-50, 550 e1-2
JO - The Journal of Allergy and Clinical Immunology
JF - The Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 3
ER -