Role of <i>Salmonella enterica</i> Lipopolysaccharide in Activation of Dendritic Cell Functions and Bacterial Containment

Zenk, Sebastian F.; Hensel, Michael

doi:10.4049/jimmunol.0900937

Cited by 31 publications

(28 citation statements)

References 47 publications

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“…2C). LPS expression is essential for the adaptation of Salmonella to an intracellular environment and its persistence within phagocytic cells (46). Consistent with this role for LPS, LPS-deficient salmonellae were unable to induce relapsing typhoid after 1 week of antibiotic treatment (Fig.…”

Section: Vol 79 2011 Protective Role Of Mlns In Relapsing Typhoid 1481supporting

confidence: 62%

Dissemination of Persistent Intestinal Bacteria via the Mesenteric Lymph Nodes Causes Typhoid Relapse

Griffin

Voedisch

et al. 2011

Infect Immun

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Enteric pathogens can cause relapsing infections in a proportion of treated patients, but greater understanding of this phenomenon is hindered by the lack of appropriate animal models. We report here a robust animal model of relapsing primary typhoid that initiates after apparently successful antibiotic treatment of susceptible mice. Four days of enrofloxacin treatment were sufficient to reduce bacterial loads below detectable levels in all major organs, and mice appeared otherwise healthy. However, any interruption of further antibiotic therapy allowed renewed fecal shedding and renewed bacterial growth in systemic tissues to occur, and mice eventually succumbed to relapsing infection. In vivo imaging of luminescent Salmonella identified the mesenteric lymph nodes (MLNs) as a major reservoir of relapsing infection. A magnetic-bead enrichment strategy isolated MLN-resident CD11b؉ Gr-1 ؊ monocytes associated with low numbers of persistent Salmonella. However, the removal of MLNs increased the severity of typhoid relapse, demonstrating that this organ serves as a protective filter to restrain the dissemination of bacteria during antibiotic therapy. Together, these data describe a robust animal model of typhoid relapse and identify an important intestinal phagocyte subset involved in protection against the systemic spread of enteric infection.

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Section: Vol 79 2011 Protective Role Of Mlns In Relapsing Typhoid 1481supporting

confidence: 62%

Dissemination of Persistent Intestinal Bacteria via the Mesenteric Lymph Nodes Causes Typhoid Relapse

Griffin

Voedisch

et al. 2011

Infect Immun

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“…For example, waaG is involved in linking the outer core to the inner core of LPS [90], [91], and when the waaQGP cluster was inactivated, uptake by human macrophages was lower compared to the wild-type strain (Figure 3), whereas a waaG ( rfaG ) mutant in S . Typhimurium shows higher uptake in murine macrophages [92], [93]. However, intracellular survival in macrophages of these mutants is lower for both serovars (Figure 3) [92], [93].…”

Section: Discussionmentioning

confidence: 94%

Selection of Salmonella enterica Serovar Typhi Genes Involved during Interaction with Human Macrophages by Screening of a Transposon Mutant Library

2012

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The human-adapted Salmonella enterica serovar Typhi (S. Typhi) causes a systemic infection known as typhoid fever. This disease relies on the ability of the bacterium to survive within macrophages. In order to identify genes involved during interaction with macrophages, a pool of approximately 105 transposon mutants of S. Typhi was subjected to three serial passages of 24 hours through human macrophages. Mutants recovered from infected macrophages (output) were compared to the initial pool (input) and those significantly underrepresented resulted in the identification of 130 genes encoding for cell membrane components, fimbriae, flagella, regulatory processes, pathogenesis, and many genes of unknown function. Defined deletions in 28 genes or gene clusters were created and mutants were evaluated in competitive and individual infection assays for uptake and intracellular survival during interaction with human macrophages. Overall, 26 mutants had defects in the competitive assay and 14 mutants had defects in the individual assay. Twelve mutants had defects in both assays, including acrA, exbDB, flhCD, fliC, gppA, mlc, pgtE, typA, waaQGP, SPI-4, STY1867-68, and STY2346. The complementation of several mutants by expression of plasmid-borne wild-type genes or gene clusters reversed defects, confirming that the phenotypic impairments within macrophages were gene-specific. In this study, 35 novel phenotypes of either uptake or intracellular survival in macrophages were associated with Salmonella genes. Moreover, these results reveal several genes encoding molecular mechanisms not previously known to be involved in systemic infection by human-adapted typhoidal Salmonella that will need to be elucidated.

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“…Salmonella enterica serovar Typhimurium interferes with the migration of intestinal DCs and hinders antigen presentation via the ubiquitination and degradation of MHC class II molecules, which prevents bacterial killing [5], [6]. Helicobacter pylori replicates within autophagosomes and retains cytosolic MHC class II molecules; H. pylori also prevents interleukin (IL)-12 production and induces IL-10 secretion, thereby inhibiting the anti-microbial Th1 response [7], [8].…”

Section: Introductionmentioning

confidence: 99%

“…Unfortunately, most of these reports are based on the comparison of naïve DCs and DCs stimulated by only one type of microorganism [5]–[7], [9]–[11], and such an approach cannot identify the elements common to microorganisms sharing cellular targets and the relative level of DC impairment. Therefore, we selected four intracellular bacteria responsible for infectious diseases in humans and that exhibit distinct lifestyles within target cells.…”

Section: Introductionmentioning

confidence: 99%

Intracellular Bacteria Interfere with Dendritic Cell Functions: Role of the Type I Interferon Pathway

Gorvel

Textoris

Banchereau³

et al. 2014

PLoS ONE

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Dendritic cells (DCs) orchestrate host defenses against microorganisms. In infectious diseases due to intracellular bacteria, the inefficiency of the immune system to eradicate microorganisms has been attributed to the hijacking of DC functions. In this study, we selected intracellular bacterial pathogens with distinct lifestyles and explored the responses of monocyte-derived DCs (moDCs). Using lipopolysaccharide as a control, we found that Orientia tsutsugamushi, the causative agent of scrub typhus that survives in the cytosol of target cells, induced moDC maturation, as assessed by decreased endocytosis activity, the ability to induce lymphocyte proliferation and the membrane expression of phenotypic markers. In contrast, Coxiella burnetii, the agent of Q fever, and Brucella abortus, the agent of brucellosis, both of which reside in vacuolar compartments, only partly induced the maturation of moDCs, as demonstrated by a phenotypic analysis. To analyze the mechanisms used by C. burnetii and B. abortus to alter moDC activation, we performed microarray and found that C. burnetii and B. abortus induced a specific signature consisting of TLR4, TLR3, STAT1 and interferon response genes. These genes were down-modulated in response to C. burnetii and B. abortus but up-modulated in moDCs activated by lipopolysaccharide and O. tsutsugamushi. This transcriptional alteration was associated with the defective interferon-β production. This study demonstrates that intracellular bacteria specifically affect moDC responses and emphasizes how C. burnetii and B. abortus interfere with moDC activation and the antimicrobial immune response. We believe that comparing infection by several bacterial species may be useful for defining new pathways and biomarkers and for developing new treatment strategies.

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Role of Salmonella enterica Lipopolysaccharide in Activation of Dendritic Cell Functions and Bacterial Containment

Cited by 31 publications

References 47 publications

Dissemination of Persistent Intestinal Bacteria via the Mesenteric Lymph Nodes Causes Typhoid Relapse

Dissemination of Persistent Intestinal Bacteria via the Mesenteric Lymph Nodes Causes Typhoid Relapse

Selection of Salmonella enterica Serovar Typhi Genes Involved during Interaction with Human Macrophages by Screening of a Transposon Mutant Library

Intracellular Bacteria Interfere with Dendritic Cell Functions: Role of the Type I Interferon Pathway

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