A quorum-sensing signal promotes host tolerance training through HDAC1-mediated epigenetic reprogramming
Arunava Bandyopadhaya1,2,3, Amy Tsurumi1,2,3, Damien Maura1,2,3
1Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
Nature Microbiology
|October 4, 2016
Summary
Pathogen Pseudomonas aeruginosa uses 2-aminoacetophenone to dampen host immunity and enable bacterial persistence. This molecule reprograms host epigenetics, creating tolerance to infection without harming the host.
Area of Science:
- Microbiology
- Immunology
- Epigenetics
Background:
- Pathogen evasion mechanisms that spare host fitness are poorly understood.
- Pseudomonas aeruginosa utilizes quorum-sensing molecule 2-aminoacetophenone to persist.
- 2-aminoacetophenone dampens host immunity and alters metabolism.
Purpose of the Study:
- To investigate how 2-aminoacetophenone induces host tissue tolerance to high bacterial loads.
- To elucidate the epigenetic mechanisms underlying this host tolerance.
Main Methods:
- Examined the regulation of histone deacetylase 1 (HDAC1) by 2-aminoacetophenone.
- Analyzed histone acetylation at pro-inflammatory cytokine loci in immune cells.
- Utilized in vivo and in vitro models to assess epigenetic reprogramming and immune response.
Main Results:
- 2-aminoacetophenone regulates HDAC1 expression and activity, leading to hypo-acetylation of histone H3.
- This epigenetic reprogramming of immune cells dampened host responses to subsequent challenges.
- The observed immunomodulatory effects were prevented by inhibiting HDAC1.
Conclusions:
- 2-aminoacetophenone induces host epigenetic reprogramming to establish tolerance to high bacterial burdens.
- This represents the first mechanistic insight into quorum-sensing molecules regulating host epigenomes for infection tolerance.
- Findings offer potential for novel preventive strategies against bacterial infections.
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