Toll-like receptors (TLRs) are primordial pathogen-recognition proteins that function as sentinels for the innate immune system. One of the TLR mysteries relates to TLR11, a receptor present in mice, but not humans, and known to recognize uropathogenic Escherichia coli. The first defined ligand for TLR11 has now been described as a profilin-like protein from Toxoplasma gondii. This discovery potentially gives us important clues as to how a gene expressed in mice, but not humans, actually relates to human infectious diseases.