Mass & Vazquez-Armendariz

Impact of developmental programming by maternal obesity on alveolar macrophage-epithelial cell interactions in lung development and function

Portrait SPP2493 member Mass
© Lutz Kettner

Elvira Mass

PI

LIMES Institute, University of Bonn

elvira(at)uni-bonn.de
website
 

 
Portrait SPP2493 member Vazquez
© Gregor Hübl

Ana Ivonne Vazquez-Armendariz

PI

LIMES Institute, University of Bonn

vazquez(at)uni-bonn.de
website

 

 

Project hypothesis

Graphic to illustrate the project hypothesis: Maternal obesity alters the intrauterine environment, leading to metabolic reprogramming of alveolar macrophages (AM) and alveolar epithelial type II cells (AECII) in the offspring. This reprogramming impacts AM development, activation, and function, as well as AECII proliferation and lung regeneration, ultimately affecting lung development and the immune response to influenza later in life.
© Mass & VazquezProject hypothesis: Maternal obesity alters the intrauterine environment, leading to metabolic reprogramming of alveolar macrophages (AM) and alveolar epithelial type II cells (AECII) in the offspring. This reprogramming impacts AM development, activation, and function, as well as AECII proliferation and lung regeneration, ultimately affecting lung development and the immune response to influenza later in life.

Project summary

Lung development and function rely on intricate interactions between immune cells and type II alveolar epithelial cells (AECII). Granulocyte-macrophage colony-stimulating factor (GM-CSF), primarily produced by distal AECII, is essential for the maintenance and functionality of alveolar macrophages (AMs) in the lung. Dysfunction or absence of AMs can lead to surfactant accumulation, causing pulmonary alveolar proteinosis, impaired immune responses to infections, and defective tissue repair and remodelling. In turn, AMs communicate with AECII through the release of cytokines and growth factors, regulating epithelial proliferation and differentiation to maintain alveolar homeostasis. Maternal obesity is an escalating public health concern, with growing evidence indicating its adverse effects on fetal lung development and an increased susceptibility to respiratory diseases in offspring. During perinatal development, maternal metabolic challenges can induce developmental programming in line with the “Developmental Origins of Health and Disease” (DOHaD) concept. Tissue-resident macrophages, such as AMs, are particularly vulnerable to maternal metabolic programming due to their long lifespan and their ability to be influenced by maternal-derived metabolites and cytokines in utero and during lactation. These environmental cues can be epigenetically imprinted onto AMs, leading to long-lasting functional alterations. This intergenerational communication may result in persistent changes in macrophage function and epithelial-immune crosstalk, predisposing offspring to inflammatory lung diseases. Despite these insights, the specific roles of AECII and AMs, and their interdependent interactions in the context of maternal metabolic disorders and their impact on lung development and infection responses remain poorly understood. In this project, we employ in vivo mouse models of maternal obesity and influenza infection, combined with a multilineage lung organoid model, to investigate the long-term effects of metabolic programming. Our goal is to dissect how maternal-derived metabolites and cytokines impact AM-AECII interactions and their responses to infection, shedding light on mechanisms that could inform future therapeutic strategies.