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Updated: Oct 27, 2025
A Mouse Model for Pathogen-induced Chronic Inflammation at Local and Systemic Sites
Published on: August 8, 2014
Postnatal inflammation in ApoE-/- mice is associated with immune training and atherosclerosis
Ellesandra C Noye1, Siroon Bekkering2,3, Albert P Limawan4,5
1School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia Queensland 4072, Australia.
Insights
Postnatal inflammation in mice primes immune cells, increasing cardiovascular disease risk. Prenatal inflammation did not worsen this effect, suggesting early life infections may offer opportunities to reduce cardiovascular risk.
Area of Science:
- Immunology
- Cardiovascular Science
- Developmental Biology
Background:
- Preterm birth elevates cardiovascular disease (CVD) risk, potentially due to prenatal inflammatory exposures like chorioamnionitis or early-life infections.
- Previous studies in ApoE-/- mice showed prenatal inflammation followed by postnatal inflammation exacerbates atherosclerosis.
- This research investigates innate immune training as a mechanism linking early-life inflammation to atherosclerosis.
Purpose of the Study:
- To determine if innate immune training contributes to atherosclerosis in a murine model.
- To assess the impact of prenatal and postnatal inflammation on immune cell responses and atherosclerosis.
- To investigate the role of lipopolysaccharide (LPS) exposure in modulating innate immunity.
Main Methods:
- Bone marrow-derived and peritoneal macrophages were isolated from ApoE-/- mice exposed to prenatal and/or postnatal lipopolysaccharide (LPS).
- Innate immune responses were evaluated via ex vivo cytokine production after toll-like receptor (TLR) agonist stimulation.
- Bone marrow progenitor populations were analyzed using flow cytometry.
Main Results:
- Postnatal LPS exposure induced a trained macrophage phenotype, characterized by heightened pro-inflammatory cytokine production upon TLR stimulation.
- Ex vivo cytokine production correlated with in vivo atherosclerosis severity.
- Prenatal LPS exposure alone did not alter cytokine production capacity, but combined exposure reduced myeloid progenitor cells.
Conclusions:
- Postnatal inflammation induces a trained immune phenotype in atherosclerosis-prone mice, independent of prenatal inflammation.
- These findings suggest that early-life infections in humans might present opportunities for interventions to mitigate cardiovascular disease risk.
Background And Aims:
Preterm birth is associated with increased risk of cardiovascular disease (CVD). This may reflect a legacy of inflammatory exposures such as chorioamnionitis which complicate pregnancies delivering preterm, or recurrent early-life infections, which are common in preterm infants. We previously reported that experimental chorioamnionitis followed by postnatal inflammation has additive and deleterious effects on atherosclerosis in ApoE-/- mice. Here, we aimed to investigate whether innate immune training is a contributory inflammatory mechanism in this murine model of atherosclerosis.
Methods:
Bone marrow-derived macrophages and peritoneal macrophages were isolated from 13-week-old ApoE-/- mice, previously exposed to prenatal intra-amniotic (experimental choriomanionitis) and/or repeated postnatal (peritoneal) lipopolysaccharide (LPS). Innate immune responses were assessed by cytokine responses following ex vivo stimulation with toll-like receptor (TLR) agonists (LPS, Pam3Cys) and RPMI for 24-h. Bone marrow progenitor populations were studied using flow cytometric analysis.
Results:
Following postnatal LPS exposure, bone marrow-derived macrophages and peritoneal macrophages produced more pro-inflammatory cytokines following TLR stimulation than those from saline-treated controls, characteristic of a trained phenotype. Cytokine production ex vivo correlated with atherosclerosis severity in vivo. Prenatal LPS did not affect cytokine production capacity. Combined prenatal and postnatal LPS exposure was associated with a reduction in populations of myeloid progenitor cells in the bone marrow.
Conclusions:
Postnatal inflammation results in a trained phenotype in atherosclerosis-prone mice that is not enhanced by prenatal inflammation. If analogous mechanisms occur in humans, then there may be novel early life opportunities to reduce CVD risk in infants with early life infections.
