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Updated: Jun 21, 2025
Investigation of Macrophage Polarization Using Bone Marrow Derived Macrophages
Published on: June 23, 2013
12,13-diHOME Promotes Inflammatory Macrophages and Epigenetically Modifies Their Capacity to Respond to Microbes and
Din L Lin1, Kevin M Magnaye1, Cara E Porsche1
1Division of Gastroenterology Department of Medicine University of California, San Francisco, CA 94143, USA.
Insights
Infant exposure to 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) alters macrophage function, increasing allergy risk. This lipid impairs antimicrobial responses and promotes inflammatory immune cell profiles, contributing to childhood atopy and asthma.
Area of Science:
- Immunology
- Microbiome research
- Environmental health
Background:
- Elevated infant fecal 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) correlates with increased childhood atopy and asthma risk.
- The precise mechanisms linking 12,13-diHOME to disease pathogenesis remain largely undefined.
- Macrophages play crucial roles in immune responses, making them potential targets for 12,13-diHOME-induced dysfunction.
Purpose of the Study:
- To investigate how 12,13-diHOME functionally and epigenetically modifies macrophages.
- To elucidate the impact of 12,13-diHOME on macrophage-mediated antimicrobial and antigen responses.
- To explore the role of 12,13-diHOME in immune cell interactions relevant to allergic sensitization.
Main Methods:
- Exposing macrophages to 12,13-diHOME in vitro.
- Assessing macrophage inflammatory profiles (IL-1β, CD206) and phagocytic capacity.
- Utilizing primary immune cell coculture assays with allergen stimulation (peanut).
- Analyzing macrophage chromatin accessibility and gene expression (interferon-stimulated response elements).
Main Results:
- 12,13-diHOME skews macrophages toward an inflammatory IL-1βhighCD206low phenotype, amplified by allergens.
- Macrophages exposed to 12,13-diHOME show reduced bacterial phagocytosis.
- In cocultures, 12,13-diHOME enhances IL-1β, IL-6 production, memory B cell expansion, and IgE levels.
- 12,13-diHOME induces epigenetic changes in macrophages, reducing interferon-regulated gene expression.
Conclusions:
- 12,13-diHOME reprograms macrophage function and B-cell interactions.
- Epigenetic modifications by 12,13-diHOME impair antimicrobial responses via the interferon axis.
- These mechanisms explain how 12,13-diHOME contributes to early-life immune dysfunction and allergic sensitization.
Abstract:
Elevated infant fecal concentrations of the bacterial-derived lipid 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) increase the risk for childhood atopy and asthma. However, the mechanisms by which this lipid contributes to disease development are largely unknown. We hypothesized that macrophages, which are key to both antimicrobial and antigen responses, are functionally and epigenetically modified by 12,13-diHOME leading to short- and long-term dysfunction with consequences for both antimicrobial and antigenic responses. Macrophages exposed to 12,13-diHOME are skewed toward inflammatory IL-1β highCD206low cells, a phenomenon that is further amplified in the presence of common microbial-, aero-, and food-allergens. These IL-1β highCD206low macrophages also exhibit reduced bacterial phagocytic capacity. In primary immune cell coculture assays involving peanut allergen stimulation, 12,13-diHOME promotes both IL-1β and IL-6 production, memory B cell expansion, and increased IgE production. Exposure to 12,13-diHOME also induces macrophage chromatin remodeling, specifically diminishing access to interferon-stimulated response elements resulting in reduced interferon-regulated gene expression upon bacterial lipopolysaccharide stimulation. Thus 12,13-diHOME reprograms macrophage effector function, B-cell interactions and promotes epigenetic modifications that exacerbate inflammatory response to allergens and mutes antimicrobial response along the interferon axis. These observations offer plausible mechanisms by which this lipid promotes early-life pathogenic microbiome development and innate immune dysfunction associated with childhood allergic sensitization.
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