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Macrophages acquire a TNF-dependent inflammatory memory in allergic asthma
Antonie Lechner1, Fiona D R Henkel1, Franziska Hartung1
1Center of Allergy and Environment (ZAUM), Technical University of Munich and Helmholtz Center Munich, Munich, Germany.
The Journal of Allergy and Clinical Immunology
|January 2, 2022
Summary
Allergic asthma patients and mice show trained macrophages with inflammatory memory. This TNF-dependent innate immune training can worsen asthma and offers a therapeutic target.
Area of Science:
- Immunology
- Allergy Research
- Innate Immunity
Background:
- Infectious agents can induce inflammatory memory in macrophages.
- It was unknown if similar trained immunity exists in type 2 inflammatory conditions like allergic asthma.
Purpose of the Study:
- To investigate macrophage-trained immunity in the context of allergic asthma.
- To decipher the mechanisms underlying persistent inflammatory responses in asthma.
Main Methods:
- Analysis of clinical samples from house dust mite (HDM)-allergic patients.
- Induction of allergic airway inflammation in mice models.
- In vitro macrophage training experiments.
- Assessment of transcriptional, metabolic, and epigenetic profiles.
Main Results:
- Macrophages from HDM-allergic individuals exhibited inflammatory transcriptional reprogramming and exaggerated mediator release.
- A shift from type 2 imprint to classical inflammatory training was observed over time.
- A TNF-dependent pathway involving 2-hydroxyglutarate (2-HG) mediated macrophage training, leading to an M2-like phenotype with high CCL17 production.
Conclusions:
- Allergen exposure induces TNF-dependent innate immune memory in macrophages.
- This trained immunity can perpetuate and exacerbate chronic type 2 airway inflammation in asthma.
- Targeting this TNF-dependent pathway presents a potential therapeutic strategy for asthma.
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