Toll-like receptors (TLRs) recognize microbial molecular signatures and can initiate innate immune responses against invading pathogens. A new study (see the related article beginning on page 1234) reports how TLR2 expression by endothelia is locally upregulated by the action of activated polymorphonuclear neutrophils via an unprecedented mechanism involving cell-cell interaction and NAD(P)H oxidase. The report reveals yet another way in which the primordial innate immune system is remarkably complex.