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

Autor: Henriette J. Scherpbier, Rob J. Vreeken, Liesbeth Van Leeuwen, Ruud Berger, Carools J. Reinecke, Gontse P. Moutloatse, Amy C. Harms, Thomas Hankemeier, Taco W. Kuijpers, Madeleine J. Bunders, Johannes C. Schoeman
Přispěvatelé: Imaging Mass Spectrometry (IMS), RS: M4I - Imaging Mass Spectrometry (IMS), AII - Amsterdam institute for Infection and Immunity, Paediatric Infectious Diseases / Rheumatology / Immunology, AII - Infectious diseases, ARD - Amsterdam Reproduction and Development, Other Research, Obstetrics and Gynaecology, Experimental Immunology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
PATAS MONKEYS
fetal development
HIV Infections
medicine.disease_cause
immune system diseases
UNINFECTED INFANTS
Homeostasis
Immunology and Allergy
Medicine
CORD BLOOD
Pregnancy Complications
Infectious
Phospholipids
Chemokine CCL3
Hypertriglyceridemia
biology
WOMEN
virus diseases
metabolomics
immune metabolism
Cholesterol
PREGNANCY
Infectious Diseases
HIV/AIDS
Female
medicine.symptom
PERINATAL EXPOSURE
Adult
Cart
Anti-HIV Agents
antiretroviral therapy
IN-UTERO
Inflammation
PERSISTENT MITOCHONDRIAL DYSFUNCTION
Proinflammatory cytokine
Major Articles and Brief Reports
03 medical and health sciences
Fetus
Immune system
Stress
Physiological
Patas monkey
Metabolome
Humans
Triglycerides
REVERSE-TRANSCRIPTASE INHIBITORS
business.industry
Infant
Newborn
Infant
Lipid metabolism
biology.organism_classification
Infectious Disease Transmission
Vertical
Chemokine CXCL10
Oxidative Stress
030104 developmental biology
Case-Control Studies
Immunology
HIV-1
Lipid Peroxidation
business
TO-CHILD TRANSMISSION
Oxidative stress
Zdroj: JOURNAL OF INFECTIOUS DISEASES
JOURNAL OF INFECTIOUS DISEASES, 216(4), 436-446
Journal of Infectious Diseases, 216(4), 436-446. Oxford University Press
The Journal of Infectious Diseases
Journal of infectious diseases, 216(4), 436-446. Oxford University Press
ISSN: 0022-1899
Popis: Summary Here, we show that the mitochondrial and lipid metabolism in uninfected infants born to HIV-1–infected women and with prenatal exposure to combination antiretroviral therapy is dysregulated and is associated with enhanced immune activation.
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.
Databáze: OpenAIRE
Externí odkaz: