Poster Presentation Asia-Pacific Vaccine and Immunotherapy Congress 2023

Maternal high fat diet predisposes the infant to systemic chronic inflammation and lung disease through IL-6 trans-signaling (#168)

Tufael Mr Ahmed 1 , Bodie Dr. Curren 1 , Simon Dr. Phipps 1
  1. Respiratory immunology, QIMRBerghofer Medical research institute, Brisbane, QLD, Australia

Poor maternal diet during pregnancy is a risk factor for severe lower respiratory tract infection (sLRI) in infancy, which in turn, is a risk factor for the development of childhood asthma. To elucidate the underlying cellular and molecular mechanisms we fed breeding-age mice a high fat diet (HFD) or control fat diet (CFD) for 3 weeks prior to conception, and inoculated the offspring with pneumonia virus of mice (PVM) at postnatal day (PND)7. To induce experimental asthma, mice were exposed to cockroach extract (CRE) between PND42 and 63.  We found that neonatal mice reared to HFD-fed mothers (‘HFD-reared pups’) developed sLRI, characterized by elevated viral load, airway remodeling, and mixed type-2/type-17 inflammation. CRE exposure in later-life induced experimental asthma in HFD- but not CFD-reared mice, but only in the HFD-fed mice that had developed sLRI in infancy. Prior to infection, HFD-reared pups developed systemic chronic inflammation (SCI), characterized by elevated innate cell numbers (neutrophils, monocytes) and inflammatory cytokines (IL-1β, IL-6, sIL-6R) in multiple organs, indicative of IL-6 trans-signaling. HFD-reared sgp130Fc transgenic pups, in which IL-6 trans-signaling is ablated, were protected against sLRI and later asthma, implicating sIL-6R. Critically, the genetic ablation of IL-6R in neutrophils, which are a rich source of sIL-6R, conferred protection to HFD-reared pups against both diseases. Taken together, our findings suggest that a maternal HFD induces neonatal SCI that predisposes to sLRI and asthma onset through neutrophil-mediated IL-6 trans-signaling.