Open AccessDissection of a type I interferon pathway in controlling bacterial intracellular infection in mice
Author(s) -
Lippmann Juliane,
Müller Holger C.,
Naujoks Jan,
Tabeling Christoph,
Shin Sunny,
Witzenrath Martin,
Hellwig Katharina,
Kirschning Carsten J.,
Taylor Gregory A.,
Barchet Winfried,
Bauer Stefan,
Suttorp Norbert,
Roy Craig R.,
Opitz Bastian
Publication year - 2011
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2011.01646.x
Subject(s) - biology , legionella pneumophila , microbiology and biotechnology , intracellular , intracellular parasite , interferon , paracrine signalling , cell type , interferon type i , immunology , receptor , cell , bacteria , genetics
Summary 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.