Cord Blood IL-12 Confers Protection to Clinical Malaria in Early Childhood Life

Yong Song; Ruth Aguilar; Jing Guo; Maria Nelia Manaca; Augusto Nhabomba; Tamara Katherine Berthoud; Siew Kim Khoo; Selma Wiertsema; Arnoldo Barbosa; Llorenç Quintó; Ingrid A. Laing; Alfredo Mayor; Caterina Guinovart; Pedro L. Alonso; Peter N. Lesouëf; Carlota Dobaño; Guicheng Brad Zhang

doi:10.1038/s41598-018-29179-y

Cord Blood IL-12 Confers Protection to Clinical Malaria in Early Childhood Life

Yong Song, Ruth Aguilar, Jing Guo, Maria Nelia Manaca, Augusto Nhabomba, Tamara Katherine Berthoud, Siew Kim Khoo, Selma Wiertsema, Arnoldo Barbosa, Llorenç Quintó, Ingrid A. Laing, Alfredo Mayor, Caterina Guinovart, Pedro L. Alonso, Peter N. Lesouëf, Carlota Dobaño, Guicheng Brad Zhang

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Abstract

Using a well-designed longitudinal cohort, we aimed to identify cytokines that were protective against malaria and to explore how they were influenced by genetic and immunological factors. 349 Mozambican pregnant women and their newborn babies were recruited and followed up for malaria outcomes until 24 months of age. Six Th1 cytokines in cord blood were screened for correlation with malaria incidence, of which IL-12 was selected for further analyses. We genotyped IL-12 polymorphisms in children/mothers and evaluated the genotype-phenotype associations and genetic effects on IL-12 levels. Maternal IL-12 concentrations were also investigated in relation to Plasmodium infections and cord blood IL-12 levels. Our data showed that high background IL-12 levels were prospectively associated with a low incidence of clinical malaria, while IL-12 production after parasite stimulation had the opposite effect on malaria incidence. IL-12 genotypes (IL-12b rs2288831/rs17860508) and the haplotype CGTTAGAG distribution were related to malaria susceptibility and background IL-12 levels. Maternal genotypes also exhibited an evident impact on host genotype-phenotype associations. Finally, a positive correlation in background IL-12 levels between maternal and cord blood was identified. Thus, cord blood background IL-12 concentrations are important for protecting children from clinical malaria, likely mediated by both genotypes (children&mothers) and maternal immunity.

Original language	English
Article number	10860
Journal	Scientific Reports
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41598-018-29179-y
Publication status	Published - 1 Dec 2018

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Song, Y., Aguilar, R., Guo, J., Manaca, M. N., Nhabomba, A., Berthoud, T. K., Khoo, S. K., Wiertsema, S., Barbosa, A., Quintó, L., Laing, I. A., Mayor, A., Guinovart, C., Alonso, P. L., Lesouëf, P. N., Dobaño, C., & Zhang, G. B. (2018). Cord Blood IL-12 Confers Protection to Clinical Malaria in Early Childhood Life. Scientific Reports, 8(1), Article 10860. https://doi.org/10.1038/s41598-018-29179-y

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title = "Cord Blood IL-12 Confers Protection to Clinical Malaria in Early Childhood Life",

abstract = "Using a well-designed longitudinal cohort, we aimed to identify cytokines that were protective against malaria and to explore how they were influenced by genetic and immunological factors. 349 Mozambican pregnant women and their newborn babies were recruited and followed up for malaria outcomes until 24 months of age. Six Th1 cytokines in cord blood were screened for correlation with malaria incidence, of which IL-12 was selected for further analyses. We genotyped IL-12 polymorphisms in children/mothers and evaluated the genotype-phenotype associations and genetic effects on IL-12 levels. Maternal IL-12 concentrations were also investigated in relation to Plasmodium infections and cord blood IL-12 levels. Our data showed that high background IL-12 levels were prospectively associated with a low incidence of clinical malaria, while IL-12 production after parasite stimulation had the opposite effect on malaria incidence. IL-12 genotypes (IL-12b rs2288831/rs17860508) and the haplotype CGTTAGAG distribution were related to malaria susceptibility and background IL-12 levels. Maternal genotypes also exhibited an evident impact on host genotype-phenotype associations. Finally, a positive correlation in background IL-12 levels between maternal and cord blood was identified. Thus, cord blood background IL-12 concentrations are important for protecting children from clinical malaria, likely mediated by both genotypes (children&mothers) and maternal immunity.",

author = "Yong Song and Ruth Aguilar and Jing Guo and Manaca, {Maria Nelia} and Augusto Nhabomba and Berthoud, {Tamara Katherine} and Khoo, {Siew Kim} and Selma Wiertsema and Arnoldo Barbosa and Lloren{\c c} Quint{\'o} and Laing, {Ingrid A.} and Alfredo Mayor and Caterina Guinovart and Alonso, {Pedro L.} and Lesou{\"e}f, {Peter N.} and Carlota Doba{\~n}o and Zhang, {Guicheng Brad}",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s41598-018-29179-y",

language = "English",

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Song, Y, Aguilar, R, Guo, J, Manaca, MN, Nhabomba, A, Berthoud, TK, Khoo, SK, Wiertsema, S, Barbosa, A, Quintó, L, Laing, IA, Mayor, A, Guinovart, C, Alonso, PL, Lesouëf, PN, Dobaño, C & Zhang, GB 2018, 'Cord Blood IL-12 Confers Protection to Clinical Malaria in Early Childhood Life', Scientific Reports, vol. 8, no. 1, 10860. https://doi.org/10.1038/s41598-018-29179-y

TY - JOUR

T1 - Cord Blood IL-12 Confers Protection to Clinical Malaria in Early Childhood Life

AU - Song, Yong

AU - Aguilar, Ruth

AU - Guo, Jing

AU - Manaca, Maria Nelia

AU - Nhabomba, Augusto

AU - Berthoud, Tamara Katherine

AU - Khoo, Siew Kim

AU - Wiertsema, Selma

AU - Barbosa, Arnoldo

AU - Quintó, Llorenç

AU - Laing, Ingrid A.

AU - Mayor, Alfredo

AU - Guinovart, Caterina

AU - Alonso, Pedro L.

AU - Lesouëf, Peter N.

AU - Dobaño, Carlota

AU - Zhang, Guicheng Brad

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Using a well-designed longitudinal cohort, we aimed to identify cytokines that were protective against malaria and to explore how they were influenced by genetic and immunological factors. 349 Mozambican pregnant women and their newborn babies were recruited and followed up for malaria outcomes until 24 months of age. Six Th1 cytokines in cord blood were screened for correlation with malaria incidence, of which IL-12 was selected for further analyses. We genotyped IL-12 polymorphisms in children/mothers and evaluated the genotype-phenotype associations and genetic effects on IL-12 levels. Maternal IL-12 concentrations were also investigated in relation to Plasmodium infections and cord blood IL-12 levels. Our data showed that high background IL-12 levels were prospectively associated with a low incidence of clinical malaria, while IL-12 production after parasite stimulation had the opposite effect on malaria incidence. IL-12 genotypes (IL-12b rs2288831/rs17860508) and the haplotype CGTTAGAG distribution were related to malaria susceptibility and background IL-12 levels. Maternal genotypes also exhibited an evident impact on host genotype-phenotype associations. Finally, a positive correlation in background IL-12 levels between maternal and cord blood was identified. Thus, cord blood background IL-12 concentrations are important for protecting children from clinical malaria, likely mediated by both genotypes (children&mothers) and maternal immunity.

AB - Using a well-designed longitudinal cohort, we aimed to identify cytokines that were protective against malaria and to explore how they were influenced by genetic and immunological factors. 349 Mozambican pregnant women and their newborn babies were recruited and followed up for malaria outcomes until 24 months of age. Six Th1 cytokines in cord blood were screened for correlation with malaria incidence, of which IL-12 was selected for further analyses. We genotyped IL-12 polymorphisms in children/mothers and evaluated the genotype-phenotype associations and genetic effects on IL-12 levels. Maternal IL-12 concentrations were also investigated in relation to Plasmodium infections and cord blood IL-12 levels. Our data showed that high background IL-12 levels were prospectively associated with a low incidence of clinical malaria, while IL-12 production after parasite stimulation had the opposite effect on malaria incidence. IL-12 genotypes (IL-12b rs2288831/rs17860508) and the haplotype CGTTAGAG distribution were related to malaria susceptibility and background IL-12 levels. Maternal genotypes also exhibited an evident impact on host genotype-phenotype associations. Finally, a positive correlation in background IL-12 levels between maternal and cord blood was identified. Thus, cord blood background IL-12 concentrations are important for protecting children from clinical malaria, likely mediated by both genotypes (children&mothers) and maternal immunity.

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U2 - 10.1038/s41598-018-29179-y

DO - 10.1038/s41598-018-29179-y

M3 - Article

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AN - SCOPUS:85050336264

SN - 2045-2322

VL - 8

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 10860

ER -

Cord Blood IL-12 Confers Protection to Clinical Malaria in Early Childhood Life

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