Intracellular <i>Salmonella</i> Inhibit Antigen Presentation by Dendritic Cells

Cheminay, Cédric; Möhlenbrink, Annette; Hensel, Michael

doi:10.4049/jimmunol.174.5.2892

Cited by 154 publications

(176 citation statements)

References 42 publications

Supporting

Mentioning

163

Contrasting

Unclassified

Order By: Relevance

“…Bacterial pathogens are known to manipulate host cell signalling cascades to promote their survival in the human intestine (Bulgin et al, 2009;Cheminay et al, 2005;Kim et al, 2005). They are known to modulate the NF-kB signalling pathway by activation or inhibition, depending on individual life cycle requirements (Rahman & McFadden, 2011).…”

Section: Discussionmentioning

confidence: 99%

Enterohaemorrhagic, but not enteropathogenic, Escherichia coli infection of epithelial cells disrupts signalling responses to tumour necrosis factor-alpha

Gareau

Brenner

et al. 2011

Microbiology

View full text Add to dashboard Cite

Enterohaemorrhagic Escherichia coli (EHEC), serotype O157 : H7 is a non-invasive, pathogenic bacterium that employs a type III secretion system (T3SS) to inject effector proteins into infected cells. In this study, we demonstrate that EHEC blocks tumour necrosis factor-alpha (TNFa)-induced NF-kB signalling in infected epithelial cells. HEK293T and INT407 epithelial cells were challenged with EHEC prior to stimulation with TNFa. Using complementary techniques, stimulation with TNFa caused activation of NF-kB, as determined by luciferase reporter assay (increase in gene expression), Western blotting (phosphorylation of IkBa), immunofluorescence (p65 nuclear translocation) and immunoassay (CXCL-8 secretion), and each was blocked by EHEC O157 : H7 infection. In contrast, subversion of host cell signalling was not observed following exposure to either enteropathogenic E. coli, strain E2348/69 (O127 : H6) or the laboratory E. coli strain HB101. Heat-killed EHEC had no effect on NF-kB activation by TNFa. Inhibition was mediated, at least in part, by Shiga toxins and by the O157 plasmid, but not by the T3SS or flagellin, as demonstrated by using isogenic mutant strains. These findings indicate the potential for developing novel therapeutic targets to interrupt the infectious process.

show abstract

Section: Discussionmentioning

confidence: 99%

Enterohaemorrhagic, but not enteropathogenic, Escherichia coli infection of epithelial cells disrupts signalling responses to tumour necrosis factor-alpha

Gareau

Brenner

et al. 2011

Microbiology

View full text Add to dashboard Cite

show abstract

“…Our findings contribute to an emerging picture of Salmonella as an enteric pathogen that has evolved numerous coordinated strategies to evade immune defense mechanisms. These strategies include the ability to (i) survive and multiply within macrophages and DC (9,38,39); (ii) induce both programmed macrophage and DC death (6,40); (iii) inhibit antigen processing and presentation by professional antigen presenting cells (30,31,36,41); and (iv), as shown in this study, directly inhibit the ability of T lymphocytes to proliferate in response to stimulation. Some of these strategies appear to be similar to strategies used by other enteric bacteria and may provide insights into how pathogens have evolved to overcome innate and adaptive host defense mechanisms.…”

Section: Spi1 Spi2 Phop Sti and The Virulence Plasmid Are Not Reqmentioning

confidence: 99%

“…5), which are unable to assemble a functional SPI2-encoded TTSS (8). Interestingly, recent evidence indicates that intracellular Salmonella can suppress MHC-II-restricted antigen presentation by professional antigen-presenting cells by means of a SPI2-dependent mechanism (30,31), suggesting that Salmonella may have evolved several independent strategies to subvert adaptive immune defense mechanisms. The observation that some type III secreted effector proteins can be translocated by either SPI1 or SPI2 TTSS (32, 33) led us to construct and test an invA spiB (SPI1 SPI2) double mutant, which expresses neither TTSS.…”

Section: Spi1 Spi2 Phop Sti and The Virulence Plasmid Are Not Reqmentioning

confidence: 99%

Salmonella inhibit T cell proliferation by a direct, contact-dependent immunosuppressive effect

Velden

Copass

Starnbach

2005

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Dendritic cells (DC) are of central importance in the initiation of T cell-mediated adaptive immunity because these professional phagocytes internalize, process, and present microbial antigens to T lymphocytes. T lymphocytes have a pivotal role in controlling and clearing infection with intracellular pathogens through cytokine production. T lymphocytes also can mediate direct lysis of infected cells or activate B and T cells. In this article, we report that DC, when cocultured with Salmonella, fail to efficiently stimulate T cells for proliferation. We show that the failure of T lymphocytes to respond to Salmonella-infected DC is not simply due to Salmonellainduced programmed DC death or interference with up-regulation of costimulatory molecules CD80 and CD86. We cocultured bacteria with purified T lymphocytes, and we demonstrate here that Salmonella have a direct, contact-dependent inhibitory effect on the T cells, even in the absence of DC. This direct, Salmonella-induced inhibitory effect reduces the ability of T cells to proliferate and produce cytokines in response to stimulation and appears to require live bacteria. Cumulatively, these results are evidence that Salmonella may interfere with the development of acquired immunity, providing insights into the complex nature of this hostpathogen interaction.bacterial interference ͉ adaptive immunity P rotection against invading microbes is coordinately regulated by innate and adaptive host defense mechanisms (1, 2). However, many microbial pathogens appear to have evolved successfully to combat, exploit, or evade host immunity (3). For example, naïve mice that are challenged with the enteric bacterium Salmonella enterica serovar Typhimurium fail to control and clear infection and succumb to an acute typhoid-like systemic illness (4). In contrast, mice previously immunized with a live-attenuated Salmonella vaccine strain are protected from lethal challenge (5), demonstrating that acquired resistance against Salmonella can develop in these hosts. It takes up to 6 wk to eradicate the vaccine strain and 60-90 days to acquire immunological memory (5). These observations suggest that adaptive immunity against Salmonella, which critically depends on the successful engagement of T lymphocytes (5), develops rather slowly.A critical step in the development of acquired resistance to intracellular bacterial pathogens is the stimulation of T lymphocytes by infected cells. The following two major subsets of T cells exist among the total population of T lymphocytes: CD4 ϩ T cells, which recognize exogenous antigens and typically are stimulated during infection with vacuolar pathogens, and CD8 ϩ T cells, which recognize cytosolic antigens and are often required to resolve infection with pathogens that escape from the vacuole and enter the host cell cytoplasm. Intriguingly, optimal protection against Salmonella, which reside in a membrane-bound compartment within infected cells, depends on both CD4 ϩ and CD8 ϩ T lymphocytes (5).To monitor the priming of T lymphocytes during Sal...

show abstract

“…MHC genes have a role in controlling infection and particular haplotypes in humans are associated with either resistance or susceptibility to typhoid fever (3). Bone marrowderived dendritic cells (DCs) infected with Salmonella show reduced ability to present antigen to T cells (4), providing further evidence that Salmonella interferes with MHC class II antigen presentation.…”

mentioning

confidence: 99%

Salmonella regulates polyubiquitination and surface expression of MHC class II antigens

Lapaque

Hutchinson²,

Jones³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Salmonella typhimurium is a facultative pathogen capable of entering and replicating in both professional and non-professional antigen presenting cells. Control of infection requires MHC class II restricted CD4 T-helper cell responses. Here we show that Salmonella infection induced polyubiquitination of HLA-DR, a post-translational modification that led to removal of mature, peptide loaded, ␣␤ dimers from the cell surface. Immature ␣␤Ii complexes were unaffected. Surface expression of all class II isotypes, HLA-DP, -DQ, and -DR, was reduced in infected cells, but other cell-surface molecules that traffic through class II peptide loading compartments were unaffected. A Salmonella strain carrying a mutation in ssaV did not induce ubiquitination of class II, implicating Salmonella T3SS-2 effector proteins in the process. T3SS-2 effectors, with established or proposed roles in ubiquitination, were not required for class II down-regulation, suggesting that an additional T3SS-2 effector is involved in regulating MHC class II ubiquitination. Although recognized as a viral immune evasion strategy, here, we demonstrate that bacteria can control surface MHC expression through ubiquitination.

show abstract

Intracellular Salmonella Inhibit Antigen Presentation by Dendritic Cells

Cited by 154 publications

References 42 publications

Enterohaemorrhagic, but not enteropathogenic, Escherichia coli infection of epithelial cells disrupts signalling responses to tumour necrosis factor-alpha

Enterohaemorrhagic, but not enteropathogenic, Escherichia coli infection of epithelial cells disrupts signalling responses to tumour necrosis factor-alpha

Salmonella inhibit T cell proliferation by a direct, contact-dependent immunosuppressive effect

Salmonella regulates polyubiquitination and surface expression of MHC class II antigens

Contact Info

Product

Resources

About