Journal
JOURNAL OF IMMUNOLOGY
Volume 190, Issue 12, Pages 6329-6339Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1300100
Keywords
-
Categories
Funding
- National Institutes of Health [AI063302, AI075039, AI080749]
- Burroughs Wellcome Fund
- Cancer Research Institute
- National Science Foundation
Ask authors/readers for more resources
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 alpha and IL-1 beta, can stimulate the type I IL-1R. IL-1 beta 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 beta in neutrophil recruitment to the lungs in response to L. pneumophila. Instead, we show that IL-1 alpha 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 alpha specifically by hematopoietic cells. In contrast to IL-1 beta, the innate signaling pathways that lead to the production of IL-1 alpha in response to L. pneumophila remain poorly defined. In particular, although we confirm a role for inflammasomes for initiation of IL-1 beta signaling in vivo, we find no essential role for inflammasomes in production of IL-1 alpha. Instead, we propose that a novel host pathway, perhaps involving inhibition of host protein synthesis, is responsible for IL-1 alpha production in response to virulent L. pneumophila. Our results establish IL-1 alpha as a critical initiator of the inflammatory response to L. pneumophila in vivo and point to an important role for IL-1 alpha in providing an alternative to inflammasome-mediated immune responses in vivo.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available