Neonatal antigen-presenting cells are functionally more quiescent in children born under traditional compared with modern environmental conditions

Lisciandro, Joanne G.; Prescott, Susan L.; Nadal-Sims, Marie G.; Devitt, Catherine J.; Richmond, Peter; Pomat, William; Siba, Peter; Holt, Patrick G.; Strickland, Deborah H.; Biggelaar, Anita H. J. van den

doi:10.1016/j.jaci.2012.06.005

Cited by 38 publications

(33 citation statements)

References 47 publications

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“…We postulate that, particularly in the neonatal period, the innate immune signalling properties ascribed to pneumolysin may predominate over that of T cell responses. We have reported previously that AUS CBMC produce higher cytokine responses to innate immune signals than PNG CBMC 26 which, as we showed in a subsequent study, is explained by the higher proportion as well as functionally more responsive status of APC in AUS compared to PNG CBMC 33, 38. We also found cord blood CD4 T cell cytokine responses to be similar in PNG and AUS CBMC when cultured in the presence of adult APC and at the same APC : T cell ratio; however, when comparing in‐vitro CBMC cultures as reported here, T cell cytokine responses may differ due to variation in the APC : T cell ratio, APC function, as well as possible earlier antigen experience of the neonatal immune system.…”

Section: Discussionsupporting

confidence: 67%

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

Francis

Richmond

Strickland

et al. 2016

Clinical and Experimental Immunology

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SummaryIn 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.

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Section: Discussionsupporting

confidence: 67%

“…We have reported previously that the relative proportion of CD4 T cells is higher in CBMC of PNG than of AUS newborns 33. We therefore explored whether the relative number of CD4 T cells present relates to the CBMC cytokine responses to PspA, dPly and PHA stimulation, as this supports that these responses would be produced by CD4 T cells.…”

Section: Resultsmentioning

confidence: 78%

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

Francis

Richmond

Strickland

et al. 2016

Clinical and Experimental Immunology

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“…Australia [88]. This was reflected by less responsiveness to stimulation in vitro in APCs from newborns born in Papua New Guinea, while they exhibited higher baseline levels of activation and inhibitory markers in the resting state compared to APC from Australian neonates [88]. This quiescent function could potentially be a protective mechanism learned in utero.…”

Section: Lactobacillus Reuteri and Toll-like Receptorsmentioning

confidence: 99%

“…Another study comparing countries with higher microbial exposure and less allergies with countries with less microbial exposure and more allergic diseases demonstrate that neonatal antigen presenting cells (APCs) are more quiescent in children born under traditional, i.e., Papua New Guinea, compared to modern environmental conditions, i.e. Australia [88]. This was reflected by less responsiveness to stimulation in vitro in APCs from newborns born in Papua New Guinea, while they exhibited higher baseline levels of activation and inhibitory markers in the resting state compared to APC from Australian neonates [88].…”

Section: Lactobacillus Reuteri and Toll-like Receptorsmentioning

confidence: 99%

Lactobacillus reuteri, Infant Allergy Prevention and Childhood Immune Maturation

Forsberg¹

2016

Probiotics and Prebiotics in Human Nutrition and Health

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The increasing allergy prevalence in affluent countries may be caused by reduced microbial stimulation, resulting in an abnormal postnatal immune maturation. This chapter concerns the theories behind the use of probiotics in randomized prevention trials, and how this supplementation affects the immunity of pregnant women, the immune development in their children, and possibly preventing allergic diseases. Most studies investigating the underlying mechanisms have focused on postnatal microbial exposure. An increasing body of evidence from studies suggests that the maternal microbial environment during pregnancy can program the immune development of the child. In human allergy intervention studies, probiotic supplementation to the mother during pregnancy, as well as to her baby postnatally, may be important for preventive effects. Also, prenatal environmental exposures may alter gene expression via epigenetic mechanisms, aiming to induce physiological adaptations to the anticipated postnatal environment. The maternal microbial environment during pregnancy may program the immune development of the child.

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“…Children born on Papa Nya Guinea compared to Australian infants have cord blood that are functionally more quiescent than Australian born neonates [218][219][220]. Evidence of differential responses to BCG-vaccination have also been presented, possibly explaining the different effect of this type of vaccination between populations [221].…”

Section: Environmental Differences In Immune Maturationmentioning

confidence: 99%

Immunomodulatory effects of probiotic supplementation during pregnancy and infancy in allergy prevention studies

Forsberg¹

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Neonatal antigen-presenting cells are functionally more quiescent in children born under traditional compared with modern environmental conditions

Cited by 38 publications

References 47 publications

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

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

Lactobacillus reuteri, Infant Allergy Prevention and Childhood Immune Maturation

Immunomodulatory effects of probiotic supplementation during pregnancy and infancy in allergy prevention studies

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