Date of this Version
Defense mechanisms against intracellular bacterial pathogens are incompletely understood. Our study characterizes a type I IFN-dependent cell-autonomous defense 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 up-regulation of IFN-stimulated genes and a cell-autonomous defense 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 defense against L. pneumophila, and demonstrates a protective role of type I IFNs in in vivo infections with intracellular bacteria.
This is the peer reviewed version of the following article: Lippman, J., Müller, H.C., Naujoks, J., Tabeling, C., Shin, S., Witzenrath, M., Hellwig, K., Kirschning, C.J., Taylor, G.A., Barchet, W., Bauer, S., Suttorp, N., Roy, C.R., and Opitz, B.: Dissection of a type I interferon pathway in controlling bacterial intracellular infection in mice. Cellular Microbiology 13(11): 1668-1682, 2011., which has been published in final form at https://dx.doi.org/10.1111/j.1462-5822.2011.01646.x. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.
Lippmann, Juliane; Müller, Holger; Naujoks, Jan; Tabeling, Christoph; Shin, Sunny; Witzenrath, Martin; Hellwig, Katharina; Kirschning, Carsten J.; Taylor, Gregory A.; Barchet, Winfried; Bauer, Stefan; Suttorp, Norbert; Roy, Craig A.; and Opitz, Bastian, "Dissection of a Type I Interferon Pathway in Controlling Bacterial Intracellular Infection in Mice" (2011). Department of Microbiology Papers. 6.
Date Posted: 09 May 2017
This document has been peer reviewed.