Developmental programming of macrophages by early life adversity
Marlene S Magalhaes1, Harry G Potter1, Anna Ahlback1
1Centre for Inflammation Research & Centre for Reproductive Health, Queens Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
Abstract:
Macrophages are central elements of all organs, where they have a multitude of physiological and pathological functions. The first macrophages are produced during fetal development, and most adult organs retain populations of fetal-derived macrophages that self-maintain without major input of hematopoietic stem cell-derived monocytes. Their developmental origins make macrophages highly susceptible to environmental perturbations experienced in early life, in particular the fetal period. It is now well recognized that such adverse developmental conditions contribute to a wide range of diseases later in life. This chapter explores the notion that macrophages are key targets of environmental adversities during development, and mediators of their long-term impact on health and disease. We first briefly summarize our current understanding of macrophage ontogeny and their biology in tissues and consider potential mechanisms by which environmental stressors may mediate fetal programming. We then review evidence for programming of macrophages by adversities ranging from maternal immune activation and diet to environmental pollutants and toxins, which have disease relevance for different organ systems. Throughout this chapter, we contemplate appropriate experimental strategies to study macrophage programming. We conclude by discussing how our current knowledge of macrophage programming could be conceptualized, and finally highlight open questions in the field and approaches to address them.
Insights
Early life environmental exposures can program macrophages, influencing long-term health and disease. This programming by fetal-derived macrophages is a key mechanism linking developmental adversities to later-life health outcomes.
Area of Science:
- Immunology
- Developmental Biology
- Environmental Health
Background:
- Macrophages are vital immune cells in all organs, originating during fetal development and self-maintaining in adults.
- Early-life environmental factors can profoundly impact macrophage development and function.
- Adverse developmental conditions are increasingly linked to a wide range of adult diseases.
Purpose of the Study:
- To explore macrophages as targets of environmental adversities during development.
- To understand how macrophages mediate the long-term health impacts of early-life exposures.
- To review evidence and experimental strategies for studying macrophage programming.
Main Methods:
- Review of current understanding of macrophage ontogeny and tissue biology.
- Analysis of mechanisms by which environmental stressors mediate fetal programming.
- Synthesis of evidence for macrophage programming by various adversities (maternal immune activation, diet, pollutants).
Main Results:
- Fetal-derived macrophages are susceptible to developmental environmental perturbations.
- Environmental adversities can program macrophages, contributing to disease later in life.
- Diverse environmental factors demonstrate disease relevance across organ systems.
Conclusions:
- Macrophages are key targets and mediators in developmental programming of health and disease.
- Understanding macrophage programming offers insights into preventing and treating environmentally linked diseases.
- Further research is needed to conceptualize and address open questions in macrophage programming.
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