Dissection of a type I interferon pathway in controlling bacterial intracellular infection in mice.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Lippmann, J; Müller, HC; Naujoks, J; Tabeling, C; Shin, S; Witzenrath, M; Hellwig, K; Kirschning, CJ; Taylor, GA; Barchet, W; Bauer, S; Suttorp, N; Roy, CR; Opitz, B

Published Date

  • November 2011

Published In

Volume / Issue

  • 13 / 11

Start / End Page

  • 1668 - 1682

PubMed ID

  • 21790939

Pubmed Central ID

  • 21790939

Electronic International Standard Serial Number (EISSN)

  • 1462-5822

Digital Object Identifier (DOI)

  • 10.1111/j.1462-5822.2011.01646.x

Language

  • eng

Conference Location

  • England