NK T cells stimulated with a ligand for TLR2 at least partly contribute to liver injury caused by <i>Escherichia coli</i> infection in mice

Hiromatsu, Takashi; Matsuguchi, Tetsuya; Shimizu, Hideyuki; Yajima, Toshiki; Nishimura, Hitoshi; Arai, Toshiyuki; Nimura, Yuji; Yoshikai, Yasunobu

doi:10.1002/eji.200324077

Cited by 17 publications

(16 citation statements)

References 30 publications

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“…and TCR␤ ϩ cells in B6 mice (38,39). In this study, we showed that TLR4 are expressed in iNKT cells by flow cytometry using permeabilized cells, while macrophages could be stained directly.…”

Section: Discussionmentioning

confidence: 56%

TLR-Dependent IL-4 Production by Invariant Vα14+Jα18+ NKT Cells to Initiate Contact Sensitivity In Vivo

Askenase

Itakura

Leite‐de‐Moraes

et al. 2005

The Journal of Immunology

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LPS stimulated B-1 cell polyclonal in vivo IgM responses depend on IL-4 release by invariant Vα14+Jα18+ NKT (iNKT) cells. The IgM Abs can recruit effector T cells to mediate contact sensitivity. LPS activates the B-1 cell response just 1 day later, and depends on CD1d, iNKT cells, IL-4, TLR4, and MyD88. LPS in vivo and in vitro stimulates rapid preferential production of IL-4 in hepatic iNKT cells within 2 h. TLR4 were demonstrated in iNKT cells by flow cytometry and functional studies. Thus, innate microbial stimulation via TLR can activate iNKT cell and B-1 cell collaboration. The result is polyclonal IgM Ab responses capable of recruiting Ag-specific T cells into tissues. This may be involved in the promotion of autoimmunity by infectious agents.

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Section: Discussionmentioning

confidence: 56%

TLR-Dependent IL-4 Production by Invariant Vα14+Jα18+ NKT Cells to Initiate Contact Sensitivity In Vivo

Askenase

Itakura

Leite‐de‐Moraes

et al. 2005

The Journal of Immunology

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“…Recent studies demonstrate that certain TLRs are expressed on various T-cell subsets, including memory T cells, natural killer T cells (NKTs) and regulatory T cells (Treg) (33)(34)(35). In addition, TLR ligands function as costimulatory factors to induce T-cell activation (36,37).…”

Section: Discussionmentioning

confidence: 99%

Activation of Toll-Like Receptor 2 Prevents Suppression of T-Cell Interferon γ Production by Modulating p38/Extracellular Signal-Regulated Kinase Pathways following Alcohol and Burn Injury

Rendón

Akhtar

et al. 2012

Mol Med

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Recent studies indicate that toll-like receptors (TLRs) are expressed on T cells and that these receptors directly or indirectly activate the adaptive immune system. We have shown previously that acute alcohol/ethanol (EtOH) intoxication combined with burn injury suppresses mesenteric lymph node (MLN) T-cell interleukin-2 (IL-2) and interferon γ (IFN-γ) production. We examined whether direct stimulation of T cells with TLR2, 4, 5 and 7 agonists modulates CD3-mediated T-cell IL-2/IFN-γ release following EtOH and burn injury. Male mice were gavaged with EtOH (2.9 gm/kg) 4 h prior to receiving an ~12.5% total body surface area sham or full-thickness burn injury. Animals were killed on d 1 after injury and T cells were purified from MLN and spleens. T cells were cultured with plate-bound anti-CD3 in the presence or absence of various TLR ligands. Although TLR2, 4 and 5 agonists potentiate anti-CD3-dependent IFN-γ by T cells, the TLR2 agonist alone induced IFN-γ production independent of CD3 stimulation. Furthermore, T cells were treated with inhibitors of myeloid differentiation primary response protein 88 (MyD88), TIR domain-containing adaptor protein (TIRAP), p38 and/or extracellular signal-regulated kinase (ERK) to determine the mechanism by which TLR2 mediates IL-2/IFN-γ production. IL-2 was not influenced by TLR agonists. MyD88 and TIRAP inhibitory peptides dose-dependently diminished the ability of T cells to release IFN-γ. p38 and ERK inhibitors also abolished TLR2-mediated T-cell IFN-γ. Together, our findings suggest that TLR2 directly modulates T-cell IFN-γ production following EtOH and burn injury, independent of antigen-presenting cells. Furthermore, we demonstrated that MyD88/TIRAP-dependent p38/ERK activation is critical to TLR2-mediated T-cell IFN-γ release following EtOH and burn injury.

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“…36 We have recently reported that natural killer T cells in the liver express Fas-ligand directly through toll-like receptors induced by gram-negative bacteria such as Salmonella choleraesuis and E. coli. 37,38 Taken together, it also seems likely that Fas-expressing Kupffer cells in BDL mice are susceptible to signals via Fas-ligand expressed on natural killer T cells after E. coli infection and predominantly produce IL-10. Further studies are needed to clarify the mechanism of predominant IL-10 production by Kupffer cells in BDL mice.…”

Section: Discussionmentioning

confidence: 99%

Kupffer cell-derived interleukin 10 is responsible for impaired bacterial clearance in bile duct-ligated mice

et al. 2004

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Extrahepatic cholestasis often evokes liver injury with hepatocyte apoptosis, aberrant cytokine production, and-most importantly-postoperative septic complications. To clarify the involvement of aberrant cytokine production and hepatocyte apoptosis in impaired resistance to bacterial infection in obstructive cholestasis, C57BL/6 mice or Fas-mutated lpr mice were inoculated intraperitoneally with 10 7 colony-forming units of Escherichia coli 5 days after bile duct ligation (BDL) or sham celiotomy. Cytokine levels in sera, liver, and immune cells were assessed via enzyme-linked immunosorbent assay or real-time reverse-transcriptase polymerase chain reaction. BDL mice showed delayed clearance of E. coli in peritoneal cavity, liver, and spleen. Significantly higher levels of serum interleukin (IL) 10 with lower levels of IL-12p40 were observed in BDL mice following E. coli infection. Interferon ␥ production from liver lymphocytes in BDL mice was not increased after E. coli infection either at the transcriptional or protein level. Kupffer cells from BDL mice produced low levels of IL-12p40 and high levels of IL-10 in vitro in response to lipopolysaccharide derived from E. coli. In vivo administration of anti-IL-10 monoclonal antibody ameliorated the course of E. coli infection in BDL mice. Furthermore, BDL-lpr mice did not exhibit impairment in E. coli killing in association with little hepatic injury and a small amount of IL-10 production. In conclusion, increased IL-10 and reciprocally suppressed IL-12 production by Kupffer cells are responsible for deteriorated resistance to bacterial infection in BDL mice. Fasmediated hepatocyte apoptosis in cholestasis may be involved in the predominant IL-10 production by Kupffer cells. (HEPATOLOGY 2004;40:414 -423.)

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NK T cells stimulated with a ligand for TLR2 at least partly contribute to liver injury caused by Escherichia coli infection in mice

Cited by 17 publications

References 30 publications

TLR-Dependent IL-4 Production by Invariant Vα14+Jα18+ NKT Cells to Initiate Contact Sensitivity In Vivo

TLR-Dependent IL-4 Production by Invariant Vα14+Jα18+ NKT Cells to Initiate Contact Sensitivity In Vivo

Activation of Toll-Like Receptor 2 Prevents Suppression of T-Cell Interferon γ Production by Modulating p38/Extracellular Signal-Regulated Kinase Pathways following Alcohol and Burn Injury

Kupffer cell-derived interleukin 10 is responsible for impaired bacterial clearance in bile duct-ligated mice

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