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Fetal Metabolic Stress Disrupts Immune Homeostasis and Induces Proinflammatory Responses in Human Immunodeficiency

Johannes C Schoeman1, Gontse P Moutloatse2, Amy C Harms1

  • 1Department of Analytical Biosciences, Leiden Academic Center for Drug Research, Leiden University, The Netherlands.

The Journal of Infectious Diseases
|June 22, 2017
PubMed

Insights

Maternal HIV-1 infection and antiretroviral therapy (ART) impact fetal development, altering infant immune metabolomes. Exposure to HIV-1 and ART in utero leads to increased inflammation and metabolic dysregulation in newborns.

Area of Science:

  • Immunology
  • Metabolomics
  • Developmental Biology

Background:

  • Infants born to mothers with Human Immunodeficiency Virus type 1 (HIV-1) on antiretroviral (ARV) therapy can experience increased morbidity and fetal growth restriction.
  • Viral infections and pharmacological interventions like ARVs can induce metabolic stress, affecting cellular immune responses and growth.

Purpose of the Study:

  • To investigate the impact of fetal exposure to HIV-1 and combination ARV therapy (cART) on the infant immune metabolome using novel metabolomic techniques.

Main Methods:

  • Utilized advanced metabolomic techniques to analyze the immune metabolome of infants exposed to cART and HIV-1 in utero.
  • Compared metabolite profiles between exposed infants and unexposed control infants.

Main Results:

  • Elevated levels of peroxidized lipids in exposed infants suggest altered mitochondrial function.
  • Dysregulated lipid metabolism observed, with increased triglycerides and decreased phospholipids in exposed infants.
  • Increased proinflammatory mediators (lysophospholipids, CXCL10, CCL3) and reduced anti-inflammatory metabolites (cytochrome P450 pathway) were found in exposed infants.

Conclusions:

  • Fetal metabolism is significantly impacted by maternal HIV-1 infection and cART.
  • In utero exposure to cART and HIV-1 skews the newborn infant's physiological immune response towards inflammation.

Keywords:
HIV-1antiretroviral therapyfetal developmentimmune metabolismmetabolomics

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