Open AccessPostnatal inflammation in ApoE−/− mice is associated with immune training and atherosclerosis
Author(s) -
Ellesandra C. Noye,
Siroon Bekkering,
Albert Prabowo Limawan,
Mike Nguyen,
Lisa K. Widiasmoko,
Hui Lü,
Salvatore Pepe,
Michael Cheung,
Trevelyan R. Menheniott,
Megan J. Wallace,
Thalia Moss,
David Burgner,
Kirsty R. Short
Publication year - 2021
Publication title -
clinical science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.91
H-Index - 138
eISSN - 1470-8736
pISSN - 0143-5221
DOI - 10.1042/cs20210496
Subject(s) - inflammation , immunology , medicine , bone marrow , cytokine , chorioamnionitis , immune system , innate immune system , progenitor cell , biology , fetus , stem cell , pregnancy , genetics
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.