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Association of Maternal Factors and HIV Infection With Innate Cytokine Responses of Delivering Mothers and Newborns in Mozambique.

ABSTRACT: Maternal factors and exposure to pathogens have an impact on infant health. For instance, HIV exposed but uninfected infants have higher morbidity and mortality than HIV unexposed infants. Innate responses are the first line of defense and orchestrate the subsequent adaptive immune response and are especially relevant in newborns. To determine the association of maternal HIV infection with maternal and newborn innate immunity we analyzed the cytokine responses upon pattern recognition receptor (PRR) stimulations in the triad of maternal peripheral and placental blood as well as in cord blood in a cohort of mother-infant pairs from southern Mozambique. A total of 48 women (35 HIV-uninfected and 13 HIV-infected) were included. Women and infant innate responses positively correlated with each other. Age, gravidity and sex of the fetus had some associations with spontaneous production of cytokines in the maternal peripheral blood. HIV-infected women not receiving antiretroviral therapy (ART) before pregnancy showed decreased IL-8 and IL-6 PRR responses in peripheral blood compared to those HIV-uninfected, and PRR hyporesponsiveness for IL-8 was also found in the corresponding infant's cord blood. HIV infection had a greater impact on placental blood responses, with significantly increased pro-inflammatory, T H 1 and T H 17 PRR responses in HIV-infected women not receiving ART before pregnancy compared to HIV-uninfected women. In conclusion, innate response of the mother and her newborn was altered by HIV infection in the women who did not receive ART before pregnancy. As these responses could be related to birth outcomes, targeted innate immune modulation could improve maternal and newborn health.

SUBMITTER: Moncunill G

PROVIDER: S-EPMC7381182 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Association of Maternal Factors and HIV Infection With Innate Cytokine Responses of Delivering Mothers and Newborns in Mozambique.

Moncunill Gemma G Dobaño Carlota C González Raquel R Smolen Kinga K KK Manaca Maria N MN Balcells Reyes R Jairoce Chenjerai C Cisteró Pau P Vala Anifa A Sevene Esperança E Rupérez María M Aponte John J JJ Macete Eusébio E Menéndez Clara C Kollmann Tobias R TR Mayor Alfredo A

Frontiers in microbiology 20200714

Maternal factors and exposure to pathogens have an impact on infant health. For instance, HIV exposed but uninfected infants have higher morbidity and mortality than HIV unexposed infants. Innate responses are the first line of defense and orchestrate the subsequent adaptive immune response and are especially relevant in newborns. To determine the association of maternal HIV infection with maternal and newborn innate immunity we analyzed the cytokine responses upon pattern recognition receptor ( ...[more]

PMID: 32765436

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Project description:BACKGROUND: Particular cytokine gene polymorphisms are involved in the regulation of the antibody production. The consequences of already described IL-4, IL-10 and IL-13 gene polymorphisms on biological parameters and antibody levels were investigated among 576 mothers at delivery and their newborns in the context of P. falciparum placental malaria infection. METHODS: The study took place in the semi-rural area of Tori-Bossito, in south-west Benin, where malaria is meso-endemic. Six biallelic polymorphisms were determined by quantitative PCR using TaqMan® Pre-Designed SNP Genotyping Assays, in IL-4 (rs2243250, rs2070874), IL-10 (rs1800896, rs1800871, rs1800872) and IL-13 (rs1800925) genes. Antibody responses directed to P. falciparum MSP-1, MSP-2, MSP-3, GLURP-R0, GLURP-R2 and AMA-1 recombinant proteins were determined by ELISA. RESULTS: The maternal IL-4(-590)*T/IL-4(+33)*T haplotype (one or two copies) was associated with favorable maternal condition at delivery (high haemoglobin levels, absence of placental parasites) and one of its component, the IL-4(-590)TT genotype, was related to low IgG levels to MSP-1, MSP-2/3D7 and MSP-2/FC27. Inversely, the maternal IL-10(-1082)AA was positively associated with P. falciparum placenta infection at delivery. As a consequence, the IL-10(-819)*T allele (in CT and TT genotypes) as well as the IL-10(-1082)*A/IL-10(-819)*T/IL-10(-592)*A haplotype (one or two copies) in which it is included, were related to an increased risk for anaemia in newborns. The maternal IL-10(-1082)AA genotype was related to high IgG levels to MSP-2/3D7 and AMA-1 in mothers and newborns, respectively. The IL-13 gene polymorphism was only involved in the newborn's antibody response to AMA-1. CONCLUSION: These data revealed that IL-4 and IL-10 maternal gene polymorphisms are likely to play a role in the regulation of biological parameters in pregnant women at delivery (anaemia, P. falciparum placenta infection) and in newborns (anaemia). Moreover, IL-4, IL-10 and IL-13 maternal gene polymorphisms were related to IgG responses to MSP-1, MSP-2/3D7 and MSP-2/FC27 in mothers as well as to AMA-1 in newborns.

Project description:RationaleStress-elicited disruption of immunity begins in utero.ObjectivesAssociations among prenatal maternal stress and cord blood mononuclear cell (CBMC) cytokine responses were prospectively examined in the Urban Environment and Childhood Asthma Study (n = 557 families).MethodsPrenatal maternal stress included financial hardship, difficult life circumstances, community violence, and neighborhood/block and housing conditions. Factor analysis produced latent variables representing three contexts: individual stressors and ecological-level strains (housing problems and neighborhood problems), which were combined to create a composite cumulative stress indicator. CBMCs were incubated with innate (lipopolysaccharide, polyinosinic-polycytidylic acid, cytosine-phosphate-guanine dinucleotides, peptidoglycan) and adaptive (tetanus, dust mite, cockroach) stimuli, respiratory syncytial virus, phytohemagglutinin, or medium alone. Cytokines were measured using multiplex ELISAs. Using linear regression, associations among increasing cumulative stress and cytokine responses were examined, adjusting for sociodemographic factors, parity, season of birth, maternal asthma and steroid use, and potential pathway variables (prenatal smoking, birth weight for gestational age).Measurements and main resultsMothers were primarily minorities (Black [71%], Latino [19%]) with an income less than $15,000 (69%). Mothers with the highest cumulative stress were older and more likely to have asthma and deliver lower birth weight infants. Higher prenatal stress was related to increased IL-8 production after microbial (CpG, PIC, peptidoglycan) stimuli and increased tumor necrosis factor-alpha to microbial stimuli (CpG, PIC). In the adaptive panel, higher stress was associated with increased IL-13 after dust mite stimulation and reduced phytohemagglutinin-induced IFN-gamma.ConclusionsPrenatal stress was associated with altered innate and adaptive immune responses in CBMCs. Stress-induced perinatal immunomodulation may impact the expression of allergic disease in these children.

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Project description:BACKGROUND:Despite increased access to treatment and reduced incidence, vertical transmission of HIV continues to pose a risk to maternal and child health in sub-Saharan Africa. Performance-based financing (PBF) directed at healthcare providers has shown potential to improve quantity and quality of maternal and child health services. However, the ways in which these PBF initiatives lead to improved service delivery are still under investigation. METHODS:Therefore, we implemented a longitudinal-controlled proof-of-concept PBF intervention at health facilities and with community-based associations focused on preventing vertical transmission of HIV (PVT) in rural Mozambique. We hypothesized that PBF would increase worker motivation and other aspects of the workplace environment in order to achieve service delivery goals. In this paper, we present two objectives from the PBF intervention with public health facilities (n=6): first, we describe the implementation of the PBF intervention and second, we assess the impact of the PBF on health worker motivation, key factors in the workplace environment, health worker satisfaction, and thoughts of leaving. Implementation (objective 1) was evaluated through quantitative service delivery data and multiple forms of qualitative data (eg, quarterly meetings, participant observation (n=120), exit interviews (n=11)). The impact of PBF on intermediary constructs (objective 2) was evaluated using these qualitative data and quantitative surveys of health workers (n=83) at intervention baseline, midline, and endline. RESULTS:We found that implementation was challenged by administrative barriers, delayed disbursement of incentives, and poor timing of evaluation relative to incentive disbursement (objective 1). Although we did not find an impact on the motivation constructs measured, PBF increased collegial support and worker empowerment, and, in a time of transitioning implementing partners, decreased against desire to leave (objective 2). CONCLUSION:Areas for future research include incentivizing meaningful quality- and process-based performance indicators and evaluating how PBF affects the pathway to service delivery, including interactions between motivation and workplace environment factors.

Dataset Information

Association of Maternal Factors and HIV Infection With Innate Cytokine Responses of Delivering Mothers and Newborns in Mozambique.

Publications

Association of Maternal Factors and HIV Infection With Innate Cytokine Responses of Delivering Mothers and Newborns in Mozambique.

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