Toll-Like Receptor 4 Dependence of Innate and Adaptive Immunity to <i>Salmonella</i>: Importance of the Kupffer Cell Network

Vázquez‐Torres, Andrés; Vallance, B; Bergman, Molly A.; Finlay, B. Brett; Cookson, Brad T.; Jones-Carson, Jessica; Fang, Ferric C.

doi:10.4049/jimmunol.172.10.6202

Cited by 159 publications

(119 citation statements)

References 39 publications

(36 reference statements)

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“…10,15 We were therefore interested in testing the hypothesis that increasing Tlr4 expression would also translate into improved control of bacterial growth in the Tlr4 overexpression and resistance to Salmonella M-F Roy et al spleen and liver of mice during infection. To verify this hypothesis, we measured the bacterial load in the spleen and liver of our mice at various time points following Salmonella infection.…”

Section: Resultsmentioning

confidence: 99%

“…These results indicate a role for the level of Tlr4 expression in controlling the bacterial replication during the first 10 days of infection. However, in F1Tg388 mice, the spleen and liver bacterial load eventually increased during the late phase of infection to reach lethal numbers around days [15][16][17][18][19][20]. Therefore, the increased protection conferred by incremental Tlr4 expression appears to be limited to the early phase of infection suggesting that despite a robust innate immune response, the host is unable to mount protective adaptive immunity resulting in long-term control of the bacterial replication.…”

Section: Resultsmentioning

confidence: 99%

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Incremental expression of Tlr4 correlates with mouse resistance to Salmonella infection and fine regulation of relevant immune genes

Larivière

Wilkinson

et al. 2006

Genes Immun

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Incremental expression of Tlr4 correlates with mouse resistance to Salmonella infection and fine regulation of relevant immune genes

Larivière

Wilkinson

et al. 2006

Genes Immun

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“…Thus, the timely development of host immune responses is critical for control of Salmonella infection. This is illustrated by the increased susceptibility of TLR4-deficient mice to Salmonella infection, in which bacterial burden increases as a result of delayed immune responses (72). It may not be necessary for a pathogen to completely abrogate host immune responses if delaying the response allows bacteria to multiply beyond the capacity of host defenses.…”

Section: Discussionmentioning

confidence: 99%

FliC-Specific CD4+ T Cell Responses Are Restricted by Bacterial Regulation of Antigen Expression

Cummings¹,

Barrett²,

Wilkerson³

et al. 2005

The Journal of Immunology

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Salmonella typhimurium, a facultatively intracellular pathogen, regulates expression of virulence factors in response to distinct environments encountered during the course of infection. We tested the hypothesis that the transition from extra- to intracellular environments during Salmonella infection triggers changes in Ag expression that impose both temporal and spatial limitations on the host T cell response. CD4+ T cells recovered from Salmonella immune mice were propagated in vitro using Ag derived from bacteria grown in conditions designed to emulate extra- or intracellular environments in vivo. Extracellular phase bacteria supported a dominant T cell response to the flagellar subunit protein FliC, whereas intracellular phase bacteria were unable to support expansion of FliC-specific T cells from populations known to contain T cells with reactivity to this Ag. This result was attributed to bacterial regulation of FliC expression: transcription and protein levels were repressed in bacteria growing in the spleens of infected mice. Furthermore, Salmonella-infected splenocytes taken directly ex vivo stimulated FliC-specific T cell clones only when intracellular FliC expression was artificially up-regulated. Although it has been suggested that a microanatomical separation of immune T cells and infected APC exists in vivo, we demonstrate that intracellular Salmonella can repress FliC expression below the T cell activation threshold. This potentially provides a mechanism for intracellular Salmonella at systemic sites to avoid detection by Ag-specific T cells primed at intestinal sites early in infection.

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“…Due to their enhanced susceptibility to Salmonella infection and the slight delay in chemokine production in the liver of i.p.-injected mice [29][30][31], we first examined cell recruitment in TLR4 À/À mice. However, no significant difference in accumulation of CD11b 1 Ly6C hi monocytes or CD11b 1 Ly6G hi neutrophils (gated as in (Fig.…”

Section: Monocytes and Neutrophils Form Inflammatory Foci In Ppmentioning

confidence: 99%

“…Moreover, the formation of cellular foci, which are preferentially made to prevent bacterial spread [40,41], is ensured by redundancy in the chemokine network. Thus, CCL2, CXCL2, CCL3 and CCL4 may all play a role in formation of cellular foci in Salmonella-infected tissues.Two of the most important candidates for initiating an immune response to Salmonella are TLR4 and TLR5 [29][30][31][42][43][44], which recognize LPS and flagellin, respectively [32]. Despite this, the Cells were stained with 7AAD, CD11c, MHC-II, Ly6C, Ly6G and a cocktail of anti-NK1.1, TCR-a/b and CD19 conjugated to the same fluorochrome and sorted into Ly6C hi Ly6G low monocytes and Ly6C int Ly6G hi neutrophils.…”

mentioning

confidence: 99%

Monocyte and neutrophil recruitment during oral Salmonella infection is driven by MyD88‐derived chemokines

Rydström

Wick

2009

Eur J Immunol

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Oral Salmonella infection recruits phagocytes to Peyer's patches (PP) and MLN. The chemokines induced in infected PP and MLN, the cellular sources during infection and the TLR signaling pathways involved in vivo are not known. Here, we show that CCL2, CXCL9 and CXCL2 mRNA are up-regulated in PP and MLN coincident with the first arrival of monocytes and neutrophils. Laser capture microdissection microscopy revealed that chemokine mRNA up-regulation was differently distributed in PP. Despite this, recruited monocytes and neutrophils formed inflammatory cell clusters throughout PP. Monocytes and neutrophils purified from infected mice preferentially produced CXCL2 and small amounts of CCL2, and neutrophils from infected mice migrated towards CXCL2 and CCL3. Furthermore, phagocyte recruitment to PP and MLN was intact in mice lacking TLR4 alone and when signaling through TLR4 and TLR5 was simultaneously absent; however, recruitment was compromised in MyD88 À/À and more so in MyD88 À/À TLR4 À/À double knockout mice. Phagocyte release into the blood, however, was only marginally reduced in MyD88 À/À TLR4 À/À mice. Defective phagocyte recruitment to PP and MLN of MyD88 À/À TLR4 À/À mice was paralleled by low chemokine induction. These data provide insight into the chemokines and TLR signaling pathways that orchestrate the early phagocyte response to oral Salmonella infection.Key words: Chemokine . Monocyte . Salmonella . TLR IntroductionMonocytes and neutrophils are critical in the first line of defense against bacteria. They develop in the bone marrow, are released into the circulation and enter tissues in response to infection. Murine monocytes in the blood are a heterogeneous population and have been divided into two main subsets based on whether they are present in steady state or recruited under inflammatory conditions [1]. Inflammatory Gr-1 hi CCR2 hi CX 3 CR1 low monocytes, which have also been called TipDC upon entering a tissue, are a source of molecules important in controlling bacterial infection, particularly iNOS and TNF-a [2][3][4].Salmonella enterica serovar Typhimurium (S. typhimurium) is a Gram-negative facultative intracellular bacterium that infects via the oral route. Orally acquired Salmonella exits the gut lumen primarily by crossing the follicle-associated epithelium overlying Peyer's patches (PP) via M cells (reviewed in [5]). The bacteria are then further spread to the MLN, most likely by DC, and to the spleen and liver via the blood [5,6]. After oral infection with S. typhimurium, neutrophils and Gr-1 hi CCR2 hi inflammatory monocytes accumulate in PP and MLN, the first organs encountering the bacteria, beginning 2-3 days after infection [3].Chemokines are the main mediators involved in the recruitment and migration of leukocytes to and within tissues. An array of chemokines is induced by inflammation and recruits monocytes, neutrophils and other cells to sites of infection. The chemokine receptors CCR2 and CXCR2 are required for monocytes and neutrophils, respectively, to egress from the bone ...

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Toll-Like Receptor 4 Dependence of Innate and Adaptive Immunity to Salmonella: Importance of the Kupffer Cell Network

Cited by 159 publications

References 39 publications

Incremental expression of Tlr4 correlates with mouse resistance to Salmonella infection and fine regulation of relevant immune genes

Incremental expression of Tlr4 correlates with mouse resistance to Salmonella infection and fine regulation of relevant immune genes

FliC-Specific CD4+ T Cell Responses Are Restricted by Bacterial Regulation of Antigen Expression

Monocyte and neutrophil recruitment during oral Salmonella infection is driven by MyD88‐derived chemokines

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