Distinct Th1- and Th2-Type Prenatal Cytokine Responses to<i>Plasmodium falciparum</i>Erythrocyte Invasion Ligands

Malhotra, Indu; Mungai, Peter; Muchiri, Eric M.; Ouma, John H.; Sharma, Shobhona; Kazura, James W.; King, Christopher L.

doi:10.1128/iai.73.6.3462-3470.2005

Cited by 84 publications

(111 citation statements)

References 60 publications

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“…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: 61%

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: 61%

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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“…These peptides were subjected to analysis by MHC class II-binding peptide prediction algorithms (Propred and Tepitope) and found to have broad binding specificity to many MHC class II alleles including DRB1*0401, DRB1*0101, and DRB1*1501 which are common in Kenya (28). A newborn was considered to be "sensitized" to MSP-1 in utero when one of the following three conditions were met: 1) by IFN-␥ ELISPOT, there were more than four cytokine-secreting cells/10 6 CBL in response to MSP-1 peptides and no secreting cells were detected in negative control wells (containing medium alone); 2) by IFN-␥ ELISPOT, in cases where cytokine-secreting cells were observed in negative control wells, the number of spots generated by MSP-1-driven CBL was 2-fold greater than control wells; 3) by ELISA for IFN-␥, IL-2, IL-5, or IL-13, net cytokine production by CBL in response to MSP-1 peptides was at least 2-fold greater than that of negative control wells (29). Using these criteria, no malaria-driven IFN-␥-secreting cells were detected in CBL from 16 healthy North American newborns or PBMC from 10 malaria-naive adults.…”

Section: Cord Blood Malaria Ag-driven T Cell Responsesmentioning

confidence: 99%

“…ELISA quantification of IL-10 production was performed on culture supernatants collected after 72 h of MSP-1 peptide stimulation of CBL as previously described (29). Ab pairs for capture and detection (all biotinylated) for IL-10 used 18551D and 18652D (BD Pharmingen).…”

Section: Il-10 Detectionmentioning

confidence: 99%

“…CBL isolated from heparin anticoagulated blood obtained from the umbilical vein were used to evaluate cytokine production in response to known T cell epitopes within the C-terminal 83-kDa fragment of MSP-1 (GYRK PLDNIKDNVGKMEDYIKK, codons 250 -271; KLNSLNNPHNVLQN FSVFFNK, codons 101-121) (27,29). Peptides were synthesized and purified to Ͼ95% (Invitrogen Life Technologies).…”

Section: Cord Blood Malaria Ag-driven T Cell Responsesmentioning

confidence: 99%

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Prenatal Malaria Immune Experience Affects Acquisition of Plasmodium falciparum Merozoite Surface Protein-1 Invasion Inhibitory Antibodies during Infancy

Dent

Malhotra

Mungai

et al. 2006

The Journal of Immunology

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African infants are often born of mothers infected with malaria during pregnancy. This can result in fetal exposure to malaria-infected erythrocytes or their soluble products with subsequent fetal immune priming or tolerance in utero. We performed a cohort study of 30 newborns from a malaria holoendemic area of Kenya to determine whether T cell sensitization to Plasmodium falciparum merozoite surface protein-1 (MSP-1) at birth correlates with infant development of anti-MSP-1 Abs acquired as a consequence of natural malaria infection. Abs to the 42- and 19-kDa C-terminal processed fragments of MSP-1 were determined by serology and by a functional assay that quantifies invasion inhibition Abs against the MSP-119 merozoite ligand (MSP-119 IIA). Infants had detectable IgG and IgM Abs to MSP-142 and MSP-119 at 6 mo of age with no significant change by age 24–30 mo. In contrast, MSP-119 IIA levels increased from 6 to 24–30 mo of age (16–29%, p < 0.01). Infants with evidence of prenatal exposure to malaria (defined by P. falciparum detection in maternal, placental, and/or cord blood compartments) and T cell sensitization at birth (defined by cord blood lymphocyte cytokine responses to MSP-1) showed the greatest age-related increase in MSP-119 IIA compared with infants with prenatal exposure to malaria but who lacked detectable T cell MSP-1 sensitization. These data suggest that fetal sensitization or tolerance to MSP-1, associated with maternal malaria infection during pregnancy, affects the development of functional Ab responses to MSP-1 during infancy.

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“…These have demonstrated low level reactivity to schizont extract, and certain blood stage Ag, and lack of reactivity to liver stage Ag [7][8][9][10][11]. Healthy adults living in malaria endemic regions generally have low level cellular reactivity to P. falciparum Ag despite lifelong exposure to parasites [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2010

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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.

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Distinct Th1- and Th2-Type Prenatal Cytokine Responses toPlasmodium falciparumErythrocyte Invasion Ligands

Abstract: Prenatal immunity to

Cited by 84 publications

References 60 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

Prenatal Malaria Immune Experience Affects Acquisition of Plasmodium falciparum Merozoite Surface Protein-1 Invasion Inhibitory Antibodies during Infancy

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

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