Histone deacetylase

Epigenetics

Virulence

Reprogramming

Immune system

Histone deacetylase 5

Gene expression

Gene

Host (biology)

Cell biology

Epigenome

Biology

DNA methylation

Histone deacetylase inhibitor

Genetics

Histone

Quorum sensing

Nature Microbiology

The mechanisms by which pathogens evade elimination without affecting host fitness are not well understood. For the pathogen Pseudomonas aeruginosa, this evasion appears to be triggered by excretion of the quorum-sensing molecule 2-aminoacetophenone, which dampens host immune responses and modulates host metabolism, thereby enabling the bacteria to persist at a high burden level. Here, we examined how 2-aminoacetophenone trains host tissues to become tolerant to a high bacterial burden, without compromising host fitness. We found that 2-aminoacetophenone regulates histone deacetylase 1 expression and activity, resulting in hypo-acetylation of lysine 18 of histone H3 at pro-inflammatory cytokine loci. Specifically, 2-aminoacetophenone induced reprogramming of immune cells occurs via alterations in histone acetylation of immune cytokines in vivo and in vitro. This host epigenetic reprograming, which was maintained for up to 7 days, dampened host responses to subsequent exposure to 2-aminoacetophenone or other u...

A quorum-sensing signal promotes host tolerance training through HDAC1-mediated epigenetic reprogramming