Infectious and sterile injuries cause the release of PAMPs and DAMPs. A study by Liu et al. (Nat. Immunol. 2019) reports that DAMP-induced sterile brain inflammation from stroke is associated with sympathetic nervous system activation, enhancing intestinal permeability, the release of microbiota-derived PAMPs, and inflammation. TREM1 is implicated as a potential target to treat stroke and DAMP- and PAMP-induced inflammation.