IL-1? signaling initiates the inflammatory response to virulent Legionella pneumophila in vivo.

ABSTRACT: Legionella pneumophila is an intracellular bacterial pathogen that is the cause of a severe pneumonia in humans called Legionnaires' disease. A key feature of L. pneumophila pathogenesis is the rapid influx of neutrophils into the lungs, which occurs in response to signaling via the IL-1R. Two distinct cytokines, IL-1? and IL-1?, can stimulate the type I IL-1R. IL-1? is produced upon activation of cytosolic sensors called inflammasomes that detect L. pneumophila in vitro and in vivo. Surprisingly, we find no essential role for IL-1? in neutrophil recruitment to the lungs in response to L. pneumophila. Instead, we show that IL-1? is a critical initiator of neutrophil recruitment to the lungs of L. pneumophila-infected mice. We find that neutrophil recruitment in response to virulent L. pneumophila requires the production of IL-1? specifically by hematopoietic cells. In contrast to IL-1?, the innate signaling pathways that lead to the production of IL-1? in response to L. pneumophila remain poorly defined. In particular, although we confirm a role for inflammasomes for initiation of IL-1? signaling in vivo, we find no essential role for inflammasomes in production of IL-1?. Instead, we propose that a novel host pathway, perhaps involving inhibition of host protein synthesis, is responsible for IL-1? production in response to virulent L. pneumophila. Our results establish IL-1? as a critical initiator of the inflammatory response to L. pneumophila in vivo and point to an important role for IL-1? in providing an alternative to inflammasome-mediated immune responses in vivo.

SUBMITTER: Barry KC 

PROVIDER: S-EPMC3682686 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature