| First Author | Barry KC | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 12 | Pages | 6329-39 |
| PubMed ID | 23686480 | Mgi Jnum | J:204844 |
| Mgi Id | MGI:5543549 | Doi | 10.4049/jimmunol.1300100 |
| Citation | Barry KC, et al. (2013) IL-1alpha signaling initiates the inflammatory response to virulent Legionella pneumophila in vivo. J Immunol 190(12):6329-39 |
| abstractText | 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-1alpha and IL-1beta, can stimulate the type I IL-1R. IL-1beta 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-1beta in neutrophil recruitment to the lungs in response to L. pneumophila. Instead, we show that IL-1alpha 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-1alpha specifically by hematopoietic cells. In contrast to IL-1beta, the innate signaling pathways that lead to the production of IL-1alpha in response to L. pneumophila remain poorly defined. In particular, although we confirm a role for inflammasomes for initiation of IL-1beta signaling in vivo, we find no essential role for inflammasomes in production of IL-1alpha. Instead, we propose that a novel host pathway, perhaps involving inhibition of host protein synthesis, is responsible for IL-1alpha production in response to virulent L. pneumophila. Our results establish IL-1alpha as a critical initiator of the inflammatory response to L. pneumophila in vivo and point to an important role for IL-1alpha in providing an alternative to inflammasome-mediated immune responses in vivo. |
