Addition of broad-spectrum HDAC inhibitors to macrophages stimulated through TLRs results in a dominant inhibition of gene expression (up to 60% of TLR-induced genes) encompassing suppression of all major functions of macrophages. Consequently, in vivo susceptibility to infections is increased when the HDAC inhibitor valproate is administered to mice, whereas overreactivity of innate immunity as observed in septic shock is decreased. (Professional illustration by Kenneth X. Probst.)