Active modification of host inflammation by<i>Salmonella</i>

Pilar, Ana Victoria C.; Reid-Yu, Sarah A.; Cooper, Colin A.; Mulder, David T.; Coombes, Brian K.

doi:10.4161/gmic.23361

Cited by 10 publications

(11 citation statements)

References 49 publications

(61 reference statements)

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“…A SifA‐deficient strain lacks SIF (Stein et al ., ) and other SIT, is defective in maintaining an intact SCV, and shows an increased release into the cytosol (Beuzon et al ., ). Other effector subsets may have roles in modification of immune responses, interference with cell migration, interference with ubiquitination, control of apoptosis and many others aspects of host–pathogen interaction (reviewed in Figueira and Holden, , Pilar et al ., ).…”

Section: Introductionmentioning

confidence: 97%

Take the tube: remodelling of the endosomal system by intracellularSalmonella enterica

Liss

Hensel

2015

Cell Microbiol

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SummarySalmonella enterica is a facultative intracellular pathogen residing in a unique host cell-derived membrane compartment, termed Salmonellacontaining vacuole or SCV. By the activity of effector proteins translocated by the SPI2-endoced type III secretion system (T3SS), the biogenesis of the SCV is manipulated to generate a habitat permissive for intracellular proliferation. By taking control of the host cell vesicle fusion machinery, intracellular Salmonella creates an extensive interconnected system of tubular membranes arising from vesicles of various origins, collectively termed Salmonella-induced tubules (SIT). Recent work investigated the dynamic properties of these manipulations. New host cell targets of SPI2-T3SS effector proteins were identified. By applying combinations of live cell imaging and ultrastructural analyses, the detailed organization of membrane compartments inhabited and modified by intracellular Salmonella is now available. These studies provided unexpected new details on the intracellular environments of Salmonella. For example, one kind of SIT, the LAMP1-positive Salmonellainduced filaments (SIF), are composed of doublemembrane tubules, with an inner lumen containing host cell cytosol and cytoskeletal filaments, and an outer lumen containing endocytosed cargo. The novel findings call for new models for the biogenesis of SCV and SIT and give raise to many open questions we discuss in this review.

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Section: Introductionmentioning

confidence: 97%

Take the tube: remodelling of the endosomal system by intracellularSalmonella enterica

Liss

Hensel

2015

Cell Microbiol

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“…33 More recently, dual RNA-seq applied to S. Typhimurium-infected epithelial cells revealed higher expression of some immunity genes positively regulated by NF-kB in infected versus uninfected cells. 34 Despite the evidence linking S. Typhimurium infection to NF-kB activation, 34,35 no study has yet characterized the NF-kB response at the single-cell level. Considering NF-kB as a dynamic and oscillatory transcription factor, we used time-lapse microscopy to capture these properties in fibroblasts persistently infected with S. Typhimurium.…”

Section: Introductionmentioning

confidence: 99%

Single-cell analyses reveal an attenuated NF-κB response in theSalmonella-infected fibroblast

et al. 2016

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The eukaryotic transcriptional regulator Nuclear Factor kappa B (NF-κB) plays a central role in the defense to pathogens. Despite this, few studies have analyzed NF-κB activity in single cells during infection. Here, we investigated at the single cell level how NF-κB nuclear localization - a proxy for NF-κB activity - oscillates in infected and uninfected fibroblasts co-existing in cultures exposed to Salmonella enterica serovar Typhimurium. Fibroblasts were used due to the capacity of S. Typhimurium to persist in this cell type. Real-time dynamics of NF-κB was examined in microfluidics, which prevents cytokine accumulation. In this condition, infected (ST+) cells translocate NF-κB to the nucleus at higher rate than the uninfected (ST-) cells. Surprisingly, in non-flow (static) culture conditions, ST- fibroblasts exhibited higher NF-κB nuclear translocation than the ST+ population, with these latter cells turning refractory to external stimuli such as TNF-α or a second infection. Sorting of ST+ and ST- cell populations confirmed enhanced expression of NF-κB target genes such as IL1B, NFKBIA, TNFAIP3, and TRAF1 in uninfected (ST-) fibroblasts. These observations proved that S. Typhimurium dampens the NF-κB response in the infected fibroblast. Higher expression of SOCS3, encoding a "suppressor of cytokine signaling," was also observed in the ST+ population. Intracellular S. Typhimurium subverts NF-κB activity using protein effectors translocated by the secretion systems encoded by pathogenicity islands 1 (T1) and 2 (T2). T1 is required for regulating expression of SOCS3 and all NF-κB target genes analyzed whereas T2 displayed no role in the control of SOCS3 and IL1B expression. Collectively, these data demonstrate that S. Typhimurium attenuates NF-κB signaling in fibroblasts, an effect only perceptible when ST+ and ST- populations are analyzed separately. This tune-down in a central host defense might be instrumental for S. Typhimurium to establish intracellular persistent infections.

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“…Owing to the initial preinflammatory phase required for Y. pestis to survive and replicate (43), our results imply that the N terminus of YscF in Y. pestis may function to interfere with host sensing in an attempt to either evade or suppress early host innate immune responses to prevent inflammation and bacterial clearance. Similar to YscF, the N terminus of PrgI may play a role to dampen the host immune response by blocking inflammation, resulting in a mechanism by which Salmonella organisms control their population density during the initial stages of infection (44). In contrast to the case with Yersinia and Salmonella, induction of immune responses leading to inflammation and subsequent neutrophil recruitment is known to promote invasion and dissemination of Shigella (3,22,23).…”

Section: Discussionmentioning

confidence: 99%

The N Terminus of Type III Secretion Needle Protein YscF from Yersinia pestis Functions To Modulate Innate Immune Responses

et al. 2015

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Active modification of host inflammation bySalmonella

Cited by 10 publications

References 49 publications

Take the tube: remodelling of the endosomal system by intracellularSalmonella enterica

Take the tube: remodelling of the endosomal system by intracellularSalmonella enterica

Single-cell analyses reveal an attenuated NF-κB response in theSalmonella-infected fibroblast

The N Terminus of Type III Secretion Needle Protein YscF from Yersinia pestis Functions To Modulate Innate Immune Responses

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