4.3 Article

A tail-specific protease is required for Legionella intracellular

Journal

CANADIAN JOURNAL OF MICROBIOLOGY
Volume -, Issue -, Pages -

Publisher

CANADIAN SCIENCE PUBLISHING
DOI: 10.1139/cjm-2022-01191

Keywords

Legionella pneumophila; intracellular multiplication; TNF-?; tail-specific protease; bone marrow-derived macrophages

Funding

  1. CIHR Open Operating Grant [142208]
  2. FRQNT Doc-toral scholarship
  3. Fonds de recherche du Quebec--Nature et technologies [RS-170946]

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Legionella pneumophila is a Gram-negative bacterium that causes Legionnaires' disease. The bacterium replicates in water systems and amoebas/ciliates, and in humans it replicates in lung cells, causing severe pneumonia. The bacteria's ability to avoid host immune responses and its production of specific enzymes are crucial for its virulence.
Legionella pneumophila 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, L. pneumophila 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 L. pneumophila proliferation. TNF-alpha is one of the major cytokines involved in this process as it renders macrophages more resistant to L. pneumophila infection and induces apoptosis of L. pneumophila-infected macrophages. Tail-specific proteases (Tsp) are involved in tolerating thermal stress and in virulence. We have previously characterized the Tsp encoded by L. pneumophila, 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 tsp is associated with higher production of TNF-alpha by macrophages in response to L. pneumophila infection. This effect is independent of the Icm/Dot secretion system.

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