title: Lack of effect of the Salmonella deubiquitinase SseL on the NF-κB pathway.
abstract: Intracellular replication of Salmonella enterica requires effector proteins translocated across the Salmonella-containing vacuolar membrane by Salmonella pathogenicity island-2 (SPI-2) encoded type III secretion system (T3SS). The SPI-2 T3SS effector SseL is a deubiquitinase that contributes to virulence in mice. Previous work has produced conflicting evidence as to the involvement of SseL in interference with the NF-κB pathway. To attempt to clarify these discrepancies, we compared mRNA levels in mouse primary bone marrow-derived macrophages infected with wild-type or sseL mutant strains using a genome-wide microarray. There was no detectable effect of loss of SseL on mRNA levels corresponding to any known NF-κB-regulated gene. In addition, there was no effect of SseL on (i) the activation or levels of both the canonical inhibitor of the NF-κB pathway (IκBα and phospho-IκBα), and the non-canonical NF-κB precursor p100/p52, (ii) the translocation of the NF-κB transcription factor p65 to the nucleus of infected macrophages and (iii) pro-inflammatory cytokines secretion. Furthermore, ectopic expression of SseL did not affect NF-κB activation in reporter cell lines. These results fail to support a role for SseL in the down-regulation of the host immune response and in particular the NF-κB pathway.
authors: Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
authors: Francisco S
authors: FS
authors: Mesquita
authors: David W
authors: DW
authors: Holden
authors: Nathalie
authors: N
authors: Rolhion
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D005786:Gene Expression Regulation; D020672:I-kappa B Proteins / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000276:immunology* / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics; D012480:Salmonella Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D019779:Salmonella enterica / Q000201:enzymology* / Q000472:pathogenicity*; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D012333:RNA, Messenger; D000072000:NF-KappaB Inhibitor alpha