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Salmonella secreted factor L deubiquitinase of Salmonella typhimurium inhibits NF-kappaB, suppresses IkappaBalpha ubiquitination and modulates innate immune responses.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2008 Apr 01; Vol. 180 (7), pp. 5045-56. - Publication Year :
- 2008
-
Abstract
- Salmonella enterica translocates virulent factors into host cells using type III secretion systems to promote host colonization, intracellular bacterial replication and survival, and disease pathogenesis. Among many effectors, the type III secretion system encoded in Salmonella pathogenicity island 2 translocates a Salmonella-specific protein, designated Salmonella secreted factor L (SseL), a putative virulence factor possessing deubiquitinase activity. In this study, we attempt to elucidate the mechanism and the function of SseL in vitro, in primary host macrophages and in vivo in infected mice. Expression of SseL in mammalian cells suppresses NF-kappaB activation downstream of IkappaBalpha kinases and impairs IkappaBalpha ubiquitination and degradation, but not IkappaBalpha phosphorylation. Disruption of the gene encoding SseL in S. enterica serovar typhimurium increases IkappaBalpha degradation and ubiquitination, as well as NF-kappaB activation in infected macrophages, compared with wild-type bacteria. Mice infected with SseL-deficient bacteria mount stronger inflammatory responses, associated with increased production of NF-kappaB-dependent cytokines. Thus, SseL represents one of the first bacterial deubiquitinases demonstrated to modulate the host inflammatory response in vivo.
- Subjects :
- Animals
Bacterial Proteins genetics
Cells, Cultured
Female
Gene Deletion
Humans
Macrophages metabolism
Mice
Mice, Inbred BALB C
Protein Binding
Salmonella Infections genetics
Salmonella Infections immunology
Salmonella Infections metabolism
Salmonella Infections pathology
Ubiquitination
Bacterial Proteins immunology
Bacterial Proteins metabolism
I-kappa B Kinase metabolism
Immunity, Innate immunology
NF-kappa B metabolism
Salmonella typhimurium enzymology
Salmonella typhimurium immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 180
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 18354230
- Full Text :
- https://doi.org/10.4049/jimmunol.180.7.5045