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

Johannes C. Schoeman, Gontse P. Moutloatse, Amy C. Harms, Rob J. Vreeken, Henriette J. Scherpbier, Liesbeth Van Leeuwen, Taco W. Kuijpers, Carools J. Reinecke, Ruud Berger, Thomas Hankemeier, Madeleine J. Bunders*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Web of Science)

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.

Original languageEnglish
Pages (from-to)436-446
Number of pages11
JournalJournal of Infectious Diseases
Volume216
Issue number4
DOIs
Publication statusPublished - 15 Aug 2017

Keywords

  • immune metabolism
  • fetal development
  • HIV-1
  • metabolomics
  • antiretroviral therapy
  • PERSISTENT MITOCHONDRIAL DYSFUNCTION
  • REVERSE-TRANSCRIPTASE INHIBITORS
  • TO-CHILD TRANSMISSION
  • IN-UTERO
  • PERINATAL EXPOSURE
  • UNINFECTED INFANTS
  • PATAS MONKEYS
  • CORD BLOOD
  • PREGNANCY
  • WOMEN

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