Dissection of a type I interferon pathway in controlling bacterial intracellular infection in mice.
Defence mechanisms against intracellular bacterial pathogens are incompletely understood. Our study characterizes a type I IFN-dependent cell-autonomous defence pathway directed against Legionella pneumophila, an intracellular model organism and frequent cause of pneumonia. We show that macrophages infected with L. pneumophila produced IFNβ in a STING- and IRF3- dependent manner. Paracrine type I IFNs stimulated upregulation of IFN-stimulated genes and a cell-autonomous defence pathway acting on replicating and non-replicating Legionella within their specialized vacuole. Our infection experiments in mice lacking receptors for type I and/or II IFNs show that type I IFNs contribute to expression of IFN-stimulated genes and to bacterial clearance as well as resistance in L. pneumophila pneumonia in addition to type II IFN. Overall, our study shows that paracrine type I IFNs mediate defence against L. pneumophila, and demonstrates a protective role of type I IFNs in in vivo infections with intracellular bacteria.
Duke Scholars
Altmetric Attention Stats
Dimensions Citation Stats
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Vacuoles
- Signal Transduction
- Microbiology
- Mice
- Membrane Proteins
- Macrophages
- Legionnaires' Disease
- Legionella pneumophila
- Interferon Type I
- Interferon Regulatory Factor-3
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Vacuoles
- Signal Transduction
- Microbiology
- Mice
- Membrane Proteins
- Macrophages
- Legionnaires' Disease
- Legionella pneumophila
- Interferon Type I
- Interferon Regulatory Factor-3