Dataset Information

Fetal Metabolic Stress Disrupts Immune Homeostasis and Induces Proinflammatory Responses in Human Immunodeficiency Virus Type 1- and Combination Antiretroviral Therapy-Exposed Infants

ABSTRACT: Increased morbidity and fetal growth restriction are reported in uninfected children born to human immunodeficiency virus type 1 (HIV-1)–infected women treated with antiretroviral (ARV) therapy. Viruses and/or pharmacological interventions such as ARVs can induce metabolic stress, skewing the cell’s immune response and restricting (cell) growth. Novel metabolomic techniques provided the opportunity to investigate the impact of fetal HIV-1 and combination ARV therapy (cART) exposure on the infants’ immune metabolome. Peroxidized lipids, generated by reactive oxygen species, were increased in cART/HIV-1–exposed infants, indicating altered mitochondrial functioning. The lipid metabolism was further dysregulated with increased triglyceride species and a subsequent decrease in phospholipids in cART/HIV-1–exposed infants compared to control infants. Proinflammatory immune mediators, lysophospholipids as well as cytokines such as CXCL10 and CCL3, were increased whereas anti-inflammatory metabolites from the cytochrome P450 pathway were reduced in cART/HIV-1–exposed infants. Taken together, these data demonstrate that the fetal metabolism is impacted by maternal factors (cART and HIV-1) and skews physiological immune responses toward inflammation in the newborn infant.

INSTRUMENT(S): 6540 Q-TOF LC/MS (Agilent), 6490 Triple Quadrupole LC/MS (Agilent)

SUBMITTER: Michael van Vliet

PROVIDER: MTBLS449 | MetaboLights | 2018-06-06

REPOSITORIES: MetaboLights

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Publications

Fetal Metabolic Stress Disrupts Immune Homeostasis and Induces Proinflammatory Responses in Human Immunodeficiency Virus Type 1- and Combination Antiretroviral Therapy-Exposed Infants.

Schoeman Johannes C JC Moutloatse Gontse P GP Harms Amy C AC Vreeken Rob J RJ Scherpbier Henriette J HJ Van Leeuwen Liesbeth L Kuijpers Taco W TW Reinecke Carools J CJ Berger Ruud R Hankemeier Thomas T Bunders Madeleine J MJ

The Journal of infectious diseases 20170801 4

Increased morbidity and fetal growth restriction are reported in uninfected children born to human immunodeficiency virus type 1 (HIV-1)-infected women treated with antiretroviral (ARV) therapy. Viruses and/or pharmacological interventions such as ARVs can induce metabolic stress, skewing the cell's immune response and restricting (cell) growth. Novel metabolomic techniques provided the opportunity to investigate the impact of fetal HIV-1 and combination ARV therapy (cART) exposure on the infant ...[more]

PMID: 28633455

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Project description:Preterm infants are susceptible to neonatal inflammatory/infective diseases requiring drug therapy. The present study hypothesized that mRNA expression in the blood may be modulated by signaling pathways during treatment. The current study aimed to explore changes in global gene expression in the blood from preterm infants with the objective of identifying patterns or pathways of potential relevance to drug therapy. The infants involved were selected based on maternal criteria indicating increased risk for therapeutic intervention. Global mRNA expression was measured in 107 longitudinal whole blood samples using Affymetrix Human Genome U133 Plus 2.0 arrays; samples were obtained from 20 preterm infants. Unsupervised clustering revealed a distinct homogeneous gene expression pattern in 13 samples derived from seven infants undergoing continuous oxygen therapy. At these sampling times, all but one of the seven infants exhibited severe drops in peripheral capillary saturation levels below 60%. The infants were reoxygenated with 100% inspired oxygen concentration. The other samples (n=94) represented the infants from the cohort at time points when they did not undergo continuous oxygen therapy. Comparing these two sets of samples identified a distinct gene expression pattern of 5,986 significantly differentially expressed genes, of which 5,167 genes exhibited reduced expression levels during transient hypoxia. This expression pattern was reversed when the infants became stable, i.e., when they were not continuously oxygenated and had no events of hypoxia. To identify signaling pathways involved in gene regulation, the Database for Annotation, Visualization and Integrated Discovery online tool was used. Mitogen activated protein kinases, which are normally induced by oxidative stress, exhibited reduced gene expression during hypoxia. In addition, nuclear factor erythroid 2 related factor 2 antioxidant response element target genes involved in oxidative stress protection were also expressed at lower levels, suggesting reduced transcription of this pathway. The findings of the present study suggest that oxidative stress dependent signaling is reduced during hypoxia. Understanding the molecular response in preterm infants during continuous oxygenation may aid in refining therapeutic strategies for oxygen therapy.

Dataset Information

Fetal Metabolic Stress Disrupts Immune Homeostasis and Induces Proinflammatory Responses in Human Immunodeficiency Virus Type 1- and Combination Antiretroviral Therapy-Exposed Infants

Publications

Fetal Metabolic Stress Disrupts Immune Homeostasis and Induces Proinflammatory Responses in Human Immunodeficiency Virus Type 1- and Combination Antiretroviral Therapy-Exposed Infants.

Similar Datasets

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