Can Prenatal Malaria Exposure Produce an Immune Tolerant Phenotype?: A Prospective Birth Cohort Study in Kenya

Malhotra, Indu; Dent, Arlene E.; Mungai, Peter; Wamachi, Alex; Ouma, John H.; Narum, David L.; Muchiri, Eric M.; Tisch, Daniel J.; King, Christopher L.

doi:10.1371/journal.pmed.1000116

Cited by 141 publications

(174 citation statements)

References 61 publications

Supporting

Mentioning

154

Contrasting

Unclassified

Order By: Relevance

“…Similar phenomena have been shown for helminths and malarial parasitic infections in pregnancy, where pathogen‐specific T cell responses induced in utero have long‐term negative consequences for the infants' susceptibility and development of immune responses to these parasites 41, 42, 43, 44, 45, 46, 47, 48, 49. Accordingly, in‐utero infection with cytomegalovirus (CMV) has been found to result in in‐utero activation of fetal CMV T cell responses that, compared to adult responses, are ‘functionally exhausted’, with a limited capacity to control CMV replication 50, 51.…”

Section: Discussionsupporting

confidence: 54%

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 54%

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

View full text Add to dashboard Cite

show abstract

“…FOXP3 1 regulatory T-cell induction could explain why PM infected children are more susceptible to malaria infections in early life [4,5], since we have shown that those with higher ex vivo Treg levels are more susceptible to subsequent infections [42]. Indeed, a recent study shows that malaria exposure in utero can lead to immune tolerance induction in some newborns characterized by a decrease in the number of individuals mounting a pro-inflammatory response and increased numbers with malaria Ag driven IL-10 production [43]. These ''tolerised'' individuals had increased susceptibility to malaria and anemia in the first 3 years of life.…”

Section: Cd25mentioning

confidence: 87%

The effect of placental malaria infection on cord blood and maternal immunoregulatory responses at birth

et al. 2010

View full text Add to dashboard Cite

Placental malaria (PM), a frequent infection of pregnancy, provides an ideal opportunity to investigate the impact on immune development of exposure of the foetal immune system to foreign Ag. We investigated the effect of PM on the regulatory phenotype and function of cord blood cells from healthy Gambian newborns and peripheral blood cells from their mothers, and analyzed for effects on the balance between regulatory and effector responses. Using the gold standard for classifying PM we further distinguished between resolved infection and acute or chronic PM active at the time of delivery. We show that exposure to malarial Ag in utero results in the expansion of malaria-specific FOXP31 Treg and more generalized FOXP3 1 CD4 1 Treg in chronic and resolved PM, alongside increased Th1 pro-inflammatory responses (IFN-c, TNF-a, IFN-c:IL-10) in resolved PM infection only. These observations demonstrate a clear effect of exposure to malarial Ag in foetal life on the immune environment at birth, with a regulatory response dominating in the newborns with ongoing chronic PM, while those with resolved infection produce both regulatory and inflammatory responses. The findings might explain some of the adverse effects on the health of babies born to women with PM.

show abstract

“…35 As a consequence of reduced muscle mass in previously MiP-exposed individuals, muscle strength might be also reduced, 36 promoting an inactive lifestyle, which is an established risk factor for diabetes, obesity and hypertension. 37 Not at last, MiPexposure is associated with an increased risk of malaria during infancy, 38 which is partly attributed to familial socioeconomic status. 39 Still, cumulative effects of early-life exposure to malaria on the metabolic health in adult age are conceivable.…”

Section: Direct Effects Of Exposure To Mip On Metabolic Traitsmentioning

confidence: 99%

In utero exposure to malaria is associated with metabolic traits in adolescence: The Agogo 2000 birth cohort study

Bedu-Addo

Alicke

Boakye-Appiah

et al. 2017

Journal of Infection

View full text Add to dashboard Cite

Summary Objectives: Malaria in pregnancy (MiP) contributes to fetal undernutrition and adverse birth outcomes, and may constitute a developmental origin of metabolic diseases in the offspring. In a Ghanaian birth cohort, we examined the relationships between MiP-exposure and metabolic traits in adolescence.Methods: MiP at delivery was assessed in 155 mother-child pairs. Among the now teenaged children (mean age, 14.8 years; 53% male), we measured fasting plasma glucose (FPG), body mass index (BMI), and systolic and diastolic blood pressure (BP). Associations of MiP with the adolescents' FPG, BMI, and BP were examined by linear regression.Results: At delivery, 45% were MiP-exposed, which increased FPG in adolescence, adjusted for mother's age at delivery, parity and familial socio-economic status (infected vs. uninfected: mean ΔFPG = 0.20 mmol/L; 95% confidence interval (CI): 0.01, 0.39; p = 0.049). As a trend, this was discernible for BP, particularly for microscopic infections (mean Δsystolic BP = 5.43 mmHg; 95% CI: 0.00, 10.88; p = 0.050; mean Δdiastolic BP = 3.67 mmHg; 95% CI: −0.81, 8.14; p = 0.107). These associations were largely independent of birth weight, gestational age and teenage BMI. Adolescent BMI was not related to MiP. Conclusions:In rural Ghana, exposure to malaria during fetal development contributes to metabolic conditions in young adulthood.

show abstract

Can Prenatal Malaria Exposure Produce an Immune Tolerant Phenotype?: A Prospective Birth Cohort Study in Kenya

Cited by 141 publications

References 61 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

The effect of placental malaria infection on cord blood and maternal immunoregulatory responses at birth

In utero exposure to malaria is associated with metabolic traits in adolescence: The Agogo 2000 birth cohort study

Contact Info

Product

Resources

About