TLRs Regulate the Gatekeeping Functions of the Intestinal Follicle-Associated Epithelium

Chabot, Sophie; Wagner, Jessica; Farrant, Stephanie; Neutra, Marian R.

doi:10.4049/jimmunol.176.7.4275

Cited by 139 publications

(123 citation statements)

References 67 publications

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“…Using laser capture microdissection, we show that CXCL2 was preferentially expressed by cells in the FAE and SED while localized production of CCL2 and CXCL9 in PP was not readily apparent. In addition, chemokine expression by the villus epithelium was not detected despite it expressing TLR [33]; the villus epithelium may have a more limited capacity to sense bacteria relative to the FAE due to the greater physical barrier overlying the villus epithelium [5,34]. Monocytes and neutrophils form clusters in PP of infected mice.…”

mentioning

confidence: 96%

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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confidence: 96%

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

Rydström

Wick

2009

Eur J Immunol

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“…Because ischemic tissue releases DAMPs, several reports have pointed to an important role for TLRs in ischemic organ damage (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). In particular, the absence of TLR2 has been shown to decrease kidney injury in response to prolonged ischemia (28) and to nephrotoxic Ab-induced glomerulonephritis (29).…”

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confidence: 99%

TLR2 Is Constitutively Expressed within the Kidney and Participates in Ischemic Renal Injury through Both MyD88-Dependent and -Independent Pathways

Shigeoka

Holscher

King

et al. 2007

The Journal of Immunology

243

220

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TLRs are an evolutionarily conserved family of cell membrane proteins believed to play a significant role in innate immunity and the response to tissue injury, including that induced by ischemia. TLR signaling pathways activate transcription factors that regulate expression of prosurvival proteins, as well as proinflammatory cytokines and chemokines through one of two proximal adapter proteins, MyD88 or Toll/IL-1R domain-containing adaptor-inducing IFN-β (Trif). Our study defines the constitutive protein expression of TLR2 in kidneys of humans and mice, and provides insight into the signaling mechanisms by which a deficiency of TLR2 protects from ischemic organ injury. Our study compared and contrasted the effects of renal ischemia in wild-type mice and mice deficient in TLR2, MyD88, Trif, and MyD88 × Trif. TLR2 protein was evident in many cell types in the kidney, including renal tubules of the outer stripe of the medulla, glomeruli, and in the renal vasculature. The pattern of protein expression was similar in humans and mice. The absence of TLR2, MyD88, and MyD88 × Trif conferred both physiologic and histologic protection against sublethal ischemia at 24 h. Interestingly, TLR2-deficient mice were better protected from ischemic renal injury than those deficient for the adapter protein MyD88, raising the intriguing possibility that TLR-2-dependent/MyD88-independent pathways also contribute to kidney injury. We conclude that TLR2 protein is constitutively expressed in the kidney and plays an important role in the pathogenesis of acute ischemic injury by signaling both MyD88-dependent and MyD88-independent pathways.

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“…It is taken up by M cells [36] and is known to possess adjuvant effects by stimulating innate immune responses by structural cell wall components [20,41,42]. In particular, yeast is able to stimulate TLR2 and 4 which have been shown to enhance microparticle uptake by M cells and to support mucosal adjuvantic properties of a carrier [2,43,44]. Moreover, it has been shown to generate adaptive (including cell-mediated) immune responses in mice after subcutaneous or oral application [19,[45][46][47] and also in humans [48].…”

Section: Surface-expression Of Yent198 Increases Targeting To the Smmentioning

confidence: 99%

Surface-modified yeast cells: A novel eukaryotic carrier for oral application

Kenngott

Kiefer

Schneider-Daum

et al. 2016

Journal of Controlled Release

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TLRs Regulate the Gatekeeping Functions of the Intestinal Follicle-Associated Epithelium

Cited by 139 publications

References 67 publications

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

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

TLR2 Is Constitutively Expressed within the Kidney and Participates in Ischemic Renal Injury through Both MyD88-Dependent and -Independent Pathways

Surface-modified yeast cells: A novel eukaryotic carrier for oral application

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