Legionella pneumophila flagellin (green) is sensed by the cytosolic sensor Naip5 in mouse macrophages.

Like many motile bacteria, Legionella pneumophila uses whip-like flagella in its natural aquatic environment. Genes that control the assembly of flagella are also required for the bug to replicate in human macrophages, a process that occurs when humans inhale aerosols from contaminated water.

In macrophages, L. pneumophila avoids degradation by blocking the fusion of bacteria-containing phagosomes with degradative lysosomes—a feat that requires its pore-forming type IV secretion system.

Molofsky and colleagues now show that the cytosolic pathogen recognition receptor Naip5—which mice require to fight off L. pneumophila—responds to bacterial flagellin. The authors think that small amounts of flagellin inadvertently leak out of the type IV secretion pores in the phagosomes. This tips off Naip5-expressing macrophages, which then trigger bacterial degradation and caspase-1–dependent cell death.

Macrophages also detected cytosolic flagellin from other bacteria, such as Salmonella typhimurium. To avoid discovery by mammalian cells, S. typhimurium turns off the expression of flagellin, which is also sensed by Toll-like receptor 5. But L. pneumophila, has had no evolutionary incentive to mask its motor, as it does not normally spread between mammals.