A tail-specific protease is required for intracellular multiplication.

is a Gram-negative bacterium found in natural and man-made water systems where it replicates within amoebas and ciliates. In humans, once inside the lungs, replicates in alveolar macrophages and causes Legionnaires' disease, a severe pneumonia. The Icm/Dot type IVb secretion system is a major virulence factor required for intracellular multiplication. The Icm/Dot system allows the secretion of effectors into the cytoplasm of the host cell. These effectors modify host cell vesicular trafficking and prevent maturation of the phagosome. The innate immune response is crucial in restricting proliferation. TNF-α is one of the major cytokines involved in this process as it renders macrophages more resistant to infection and induces apoptosis of -infected macrophages. Tail-specific proteases (Tsp) are involved in tolerating thermal stress and in virulence. We have previously characterized the Tsp encoded by , showing that it is important for surviving thermal stress and for infection of amoeba when a temperature change occurs during infection. Here, we demonstrated that Tsp is required for intracellular multiplication in macrophages. Absence of is associated with higher production of TNF-α by macrophages in response to infection. This effect is independent of the Icm/Dot secretion system.