IL-10 expression in macrophages from neonates born from obese mothers is suppressed by IL-4 and LPS/INFγ
Francisca Cifuentes-Zúñiga1, Viviana Arroyo-Jousse1, Gustavo Soto-Carrasco1
1Division of Pediatrics, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
Insights
Maternal obesity alters offspring immune cells, leading to a basal anti-inflammatory state in neonatal macrophages. This suggests intrauterine programming of immune function due to maternal obesity.
Area of Science:
- Immunology
- Developmental Biology
- Epigenetics
Background:
- Offspring of obese mothers face increased chronic disease risk.
- Altered immune function is linked to maternal obesity.
- Neonatal immune cell programming is critical for long-term health.
Purpose of the Study:
- Investigate maternal obesity's impact on neonatal monocyte-derived macrophages.
- Analyze gene expression and DNA methylation of inflammatory genes.
- Assess pro- and anti-inflammatory responses in macrophages.
Main Methods:
- Cord blood collection from newborns of obese and lean mothers.
- Isolation and differentiation of monocytes into macrophages.
- Quantitative PCR for mRNA levels and pyrosequencing for DNA methylation.
Main Results:
- Obese mothers' offspring showed altered mRNA levels for key inflammatory cytokines (e.g., IL-1β, IL-10, TNFα).
- Macrophages from obese offspring exhibited an unbalanced response to M1 and M2 polarization stimuli.
- DNA methylation changes in inflammatory genes paralleled altered gene expression, suggesting intrauterine programming.
Conclusions:
- Maternal obesity leads to a basal anti-inflammatory phenotype in neonatal macrophages.
- Epigenetic modifications, specifically DNA methylation, may mediate immune programming by maternal obesity.
- These findings highlight a potential mechanism for increased chronic disease risk in offspring of obese mothers.
Abstract:
Obese women offspring have a higher risk of developing chronic diseases associated with an altered immune function. We aim to determine, in neonatal monocyte-derived macrophages, whether maternal obesity is associated with an altered expression and DNA methylation of pro- and anti-inflammatory genes, along with a higher pro-inflammatory response. Cord blood from newborns of obese (Ob) and lean (control) women were obtained at delivery. Monocytes were isolated and differentiated into macrophages, in which M1 (LPS/IFNγ) and M2 (IL-4) polarization were assayed. The mRNA levels for TNFα, IL-1β, IL-12A, IL-12B, IL-10, and IL-4R were quantified by qPCR and the DNA methylation of candidate genes determined by pyrosequencing.
Results:
Ob-monocytes had decreased levels of mRNA for pro-inflammatory cytokines IL-1β, IL-10, and IL-12B compared with controls. Conversely, Ob-macrophages showed increased levels of mRNA for TNFα, IL-4R, and IL-10 compared with controls. M1 response was comparable between both groups, characterized by an important induction of TNFα and IL-1β. In response to an M2 stimulus, control macrophages showed a decreased expression of inflammatory mediators while Ob-macrophages had an additional suppression of the anti-inflammatory mediator IL-10. Changes in IL-1β (monocytes) and IL-10 (macrophages) in Ob-monocytes were paralleled by changes in their promoter DNA methylation in fetal monocytes. These results suggest that monocyte-derived macrophages from obese newborns show a basal anti-inflammatory phenotype with an unbalanced response to M1 and M2 polarization stimuli. The presence of changes in DNA methylation of key inflammatory genes in neonatal monocytes suggests an intrauterine programing of immune function by maternal obesity.
