Placental malaria is associated with attenuated CD4 T-cell responses to tuberculin PPD 12 months after BCG vaccination

Brigitte Walther; David J C Miles; Pauline Waight; Melba S Palmero; Olubukola Ojuola; Ebrima S Touray; Hilton Whittle; Marianne van der Sande; Sarah Crozier; Katie L Flanagan

doi:10.1186/1471-2334-12-6

Placental malaria is associated with attenuated CD4 T-cell responses to tuberculin PPD 12 months after BCG vaccination

Brigitte Walther, David J C Miles, Pauline Waight, Melba S Palmero, Olubukola Ojuola, Ebrima S Touray, Hilton Whittle, Marianne van der Sande, Sarah Crozier, Katie L Flanagan

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: Placental malaria (PM) is associated with prenatal malaise, but many PM+ infants are born without symptoms. As malaria has powerful immunomodulatory effects, we tested the hypothesis that PM predicts reduced T-cell responses to vaccine challenge.

METHODS: We recruited healthy PM+ and PM- infants at birth. At six and 12 months, we stimulated PBMCs with tuberculin purified protein derivative (PPD) and compared expression of CD154, IL-2 and IFNγ by CD4 T-cells to a negative control using flow cytometry.We measured the length, weight and head circumference at birth and 12 months.

RESULTS: IL-2 and CD154 expression were low in both groups at both timepoints, without discernable differences. Expression of IFNγ was similarly low at 6 months but by 12 months, the median response was higher in PM- than PM + infants (p = 0.026). The PM+ infants also had a lower weight (p = 0.032) and head circumference (p = 0.041) at 12 months, indicating lower growth rates.At birth, the size and weight of the PM+ and PM- infants were equivalent. By 12 months, the PM+ infants had a lower weight and head circumference than the PM- infants.

CONCLUSIONS: Placental malaria was associated with reduced immune responses 12 months after immune challenge in infants apparently healthy at birth.

Original language	English
Pages (from-to)	6
Journal	BMC Infectious Diseases [E]
Volume	12
DOIs	https://doi.org/10.1186/1471-2334-12-6
Publication status	Published - 2012

Keywords

CD4-Positive T-Lymphocytes
CD40 Ligand
Cells, Cultured
Female
Flow Cytometry
Humans
Infant
Infant, Newborn
Interferon-gamma
Interleukin-2
Leukocytes, Mononuclear
Malaria
Placenta Diseases
Pregnancy
Tuberculin
Tuberculin Test
Tuberculosis Vaccines

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10.1186/1471-2334-12-6

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@article{fc4c725ca7674888bf9464a2f9f21705,

title = "Placental malaria is associated with attenuated CD4 T-cell responses to tuberculin PPD 12 months after BCG vaccination",

abstract = "BACKGROUND: Placental malaria (PM) is associated with prenatal malaise, but many PM+ infants are born without symptoms. As malaria has powerful immunomodulatory effects, we tested the hypothesis that PM predicts reduced T-cell responses to vaccine challenge.METHODS: We recruited healthy PM+ and PM- infants at birth. At six and 12 months, we stimulated PBMCs with tuberculin purified protein derivative (PPD) and compared expression of CD154, IL-2 and IFNγ by CD4 T-cells to a negative control using flow cytometry.We measured the length, weight and head circumference at birth and 12 months.RESULTS: IL-2 and CD154 expression were low in both groups at both timepoints, without discernable differences. Expression of IFNγ was similarly low at 6 months but by 12 months, the median response was higher in PM- than PM + infants (p = 0.026). The PM+ infants also had a lower weight (p = 0.032) and head circumference (p = 0.041) at 12 months, indicating lower growth rates.At birth, the size and weight of the PM+ and PM- infants were equivalent. By 12 months, the PM+ infants had a lower weight and head circumference than the PM- infants.CONCLUSIONS: Placental malaria was associated with reduced immune responses 12 months after immune challenge in infants apparently healthy at birth.",

keywords = "CD4-Positive T-Lymphocytes, CD40 Ligand, Cells, Cultured, Female, Flow Cytometry, Humans, Infant, Infant, Newborn, Interferon-gamma, Interleukin-2, Leukocytes, Mononuclear, Malaria, Placenta Diseases, Pregnancy, Tuberculin, Tuberculin Test, Tuberculosis Vaccines",

author = "Brigitte Walther and Miles, \{David J C\} and Pauline Waight and Palmero, \{Melba S\} and Olubukola Ojuola and Touray, \{Ebrima S\} and Hilton Whittle and \{van der Sande\}, Marianne and Sarah Crozier and Flanagan, \{Katie L\}",

year = "2012",

doi = "10.1186/1471-2334-12-6",

language = "English",

volume = "12",

pages = "6",

journal = "BMC Infectious Diseases [E]",

issn = "1471-2334",

publisher = "BioMed Central",

}

TY - JOUR

T1 - Placental malaria is associated with attenuated CD4 T-cell responses to tuberculin PPD 12 months after BCG vaccination

AU - Walther, Brigitte

AU - Miles, David J C

AU - Waight, Pauline

AU - Palmero, Melba S

AU - Ojuola, Olubukola

AU - Touray, Ebrima S

AU - Whittle, Hilton

AU - van der Sande, Marianne

AU - Crozier, Sarah

AU - Flanagan, Katie L

PY - 2012

Y1 - 2012

N2 - BACKGROUND: Placental malaria (PM) is associated with prenatal malaise, but many PM+ infants are born without symptoms. As malaria has powerful immunomodulatory effects, we tested the hypothesis that PM predicts reduced T-cell responses to vaccine challenge.METHODS: We recruited healthy PM+ and PM- infants at birth. At six and 12 months, we stimulated PBMCs with tuberculin purified protein derivative (PPD) and compared expression of CD154, IL-2 and IFNγ by CD4 T-cells to a negative control using flow cytometry.We measured the length, weight and head circumference at birth and 12 months.RESULTS: IL-2 and CD154 expression were low in both groups at both timepoints, without discernable differences. Expression of IFNγ was similarly low at 6 months but by 12 months, the median response was higher in PM- than PM + infants (p = 0.026). The PM+ infants also had a lower weight (p = 0.032) and head circumference (p = 0.041) at 12 months, indicating lower growth rates.At birth, the size and weight of the PM+ and PM- infants were equivalent. By 12 months, the PM+ infants had a lower weight and head circumference than the PM- infants.CONCLUSIONS: Placental malaria was associated with reduced immune responses 12 months after immune challenge in infants apparently healthy at birth.

AB - BACKGROUND: Placental malaria (PM) is associated with prenatal malaise, but many PM+ infants are born without symptoms. As malaria has powerful immunomodulatory effects, we tested the hypothesis that PM predicts reduced T-cell responses to vaccine challenge.METHODS: We recruited healthy PM+ and PM- infants at birth. At six and 12 months, we stimulated PBMCs with tuberculin purified protein derivative (PPD) and compared expression of CD154, IL-2 and IFNγ by CD4 T-cells to a negative control using flow cytometry.We measured the length, weight and head circumference at birth and 12 months.RESULTS: IL-2 and CD154 expression were low in both groups at both timepoints, without discernable differences. Expression of IFNγ was similarly low at 6 months but by 12 months, the median response was higher in PM- than PM + infants (p = 0.026). The PM+ infants also had a lower weight (p = 0.032) and head circumference (p = 0.041) at 12 months, indicating lower growth rates.At birth, the size and weight of the PM+ and PM- infants were equivalent. By 12 months, the PM+ infants had a lower weight and head circumference than the PM- infants.CONCLUSIONS: Placental malaria was associated with reduced immune responses 12 months after immune challenge in infants apparently healthy at birth.

KW - CD4-Positive T-Lymphocytes

KW - CD40 Ligand

KW - Cells, Cultured

KW - Female

KW - Flow Cytometry

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Interferon-gamma

KW - Interleukin-2

KW - Leukocytes, Mononuclear

KW - Malaria

KW - Placenta Diseases

KW - Pregnancy

KW - Tuberculin

KW - Tuberculin Test

KW - Tuberculosis Vaccines

U2 - 10.1186/1471-2334-12-6

DO - 10.1186/1471-2334-12-6

M3 - Article

C2 - 22243970

SN - 1471-2334

VL - 12

SP - 6

JO - BMC Infectious Diseases [E]

JF - BMC Infectious Diseases [E]

ER -

Placental malaria is associated with attenuated CD4 T-cell responses to tuberculin PPD 12 months after BCG vaccination

Abstract

Keywords

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