Cellular Recognition of Trimyristoylated Peptide or Enterobacterial Lipopolysaccharide via Both TLR2 and TLR4

Spiller, Stephan; Dreher, Stefan; Meng, Guangxun; Grabiec, Alina; Thomas, Winston; Hartung, Thomas; Pfeffer, Klaus; Hochrein, Hubertus; Brade, Helmut; Bessler, Wolfgang G.; Wagner, Hermann; Kirschning, Carsten J.

doi:10.1074/jbc.m610340200

Cited by 41 publications

(31 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also observed that Salmonella LPSinduced responses were reduced in TLR2 Ϫ/Ϫ DCs relative to those in WT cells. This may be due to the contamination of this particular commercial preparation of LPS with certain TLR2 ligands from bacteria (1,16) or LPS itself signaling through TLR2, besides the expected TLR4, as reported previously (43).…”

Section: Resultssupporting

confidence: 53%

Campylobacter jejuni -Induced Activation of Dendritic Cells Involves Cooperative Signaling through Toll-Like Receptor 4 (TLR4)-MyD88 and TLR4-TRIF Axes

Rathinam

Appledorn²,

Hoag

et al. 2009

Infect Immun

View full text Add to dashboard Cite

Campylobacter jejuni is an important cause of human enteritis and has been linked to the development of autoimmune diseases. Recently we showed that infection of murine dendritic cells (DCs) with C. jejuni resulted in DC activation and induction of Campylobacter-specific Th1-effector responses. Toll-like receptor (TLR) signaling through myeloid differentiation factor 88 (MyD88) and/or Toll-interleukin 1 (IL-1) receptor domaincontaining adaptor-inducing beta interferon (IFN-␤) (TRIF) is critical in inducing immunity against pathogens. In this study, we investigated the role of TLR2, TLR4, MyD88, and TRIF signaling in C. jejuni-induced inflammatory activation of DCs. DC upregulation of major histocompatibility complex class II and costimulatory molecules after C. jejuni challenge was profoundly impaired by TLR2, TLR4, MyD88, and TRIF deficiencies. Similarly, C. jejuni-induced secretion of IL-12, IL-6, and tumor necrosis factor alpha was significantly inhibited in TLR2 ؊/؊ , TLR4 ؊/؊ , MyD88 ؊/؊ , and TRIF ؊/؊ DCs compared to that in wild-type DCs; however, the magnitude of inhibition was greater in MyD88 ؊/؊ , TRIF ؊/؊ , and TLR4 ؊/؊ DCs than in TLR2؊/؊ DCs. Furthermore, C. jejuni induced interferon regulatory factor 3 phosphorylation and IFN-␤ secretion by DCs in a TLR4-TRIF-dependent fashion, further demonstrating activation of this pathway by C. jejuni. Importantly, TLR2, TLR4, MyD88, and TRIF deficiencies all markedly impaired the Th1-priming ability of C. jejuni-infected DCs. Thus, our results show that cooperative signaling through the TLR4-MyD88 and TLR4-TRIF axes represents a novel mechanism mediating C. jejuni-induced inflammatory responses of DCs. To our knowledge, such a mechanism has not been demonstrated previously for an intact bacterium.

show abstract

Section: Resultssupporting

confidence: 53%

Campylobacter jejuni -Induced Activation of Dendritic Cells Involves Cooperative Signaling through Toll-Like Receptor 4 (TLR4)-MyD88 and TLR4-TRIF Axes

Rathinam

Appledorn²,

Hoag

et al. 2009

Infect Immun

View full text Add to dashboard Cite

show abstract

“…Unlike a previous report that indicates the presence of only TLR4 and TLR5 in hen granulosa cells (Subdei et al 2007), TLR4, TLR2, and TLR15 mRNAs were detected in both undifferentiated and differentiated granulosa cells from hen follicles. This finding is significant, because TLR4 and TLR2 (type 2) have been shown to recognize bacterial LPS (Fukui et al 2001, Spiller et al 2007. Additionally, while genes encoding key chicken TLR-signaling components have been identified in silico, this is the first study to verify their presence in granulosa cells.…”

Section: Discussionmentioning

confidence: 89%

Toll-like receptor signaling in hen ovarian granulosa cells is dependent on stage of follicle maturation

2009

View full text Add to dashboard Cite

The recent identification of toll-like receptor (TLR) signaling within ovarian granulosa cells has broad implications for ovarian physiology. Functions of TLRs within granulosa cells of the laying hen are of particular interest due to the method of transovarian transmission of Salmonella enteritidis, which results in egg contamination. This study utilized hen granulosa cells to evaluate the expression and function of Gallus TLR-signaling at distinct stages of follicular maturity. Data presented herein demonstrate the presence of TLR2, TLR4, and TLR15 mRNAs in undifferentiated granulosa cells from prehierarchal follicles and differentiated granulosa cells from preovulatory follicles, together with mRNAs encoding adaptor proteins and signaling components required for TLR signaling gene. Treatment with lipopolysaccharide (LPS) or LH, in vitro, led to the differential regulation of TLRs based on the stage of follicle maturation, with the largest (F1) follicle granulosa cells having the most rapid response. Furthermore, treatment with LPS resulted in attenuation of agonistinduced progesterone synthesis in undifferentiated, but not differentiated, granulosa cells. Additionally, undifferentiated granulosa cells were significantly more sensitive to LPS-induced apoptosis than differentiated granulosa cells from the F1 follicle. Together, these data provide evidence for a complete and functional TLR signaling pathway in hen granulosa cells, with effects on steroidogenesis and cell viability dependent upon stage of maturation. These differences may reflect the susceptibility of granulosa cells at early stages of maturation to undergo apoptosis in response to select pathogenic stimuli, thus attenuating transovarian transmission, whereas granulosa cells from preovulatory follicles are comparably resistant to LPS-mediated apoptosis. Reproduction (2009) 137 987-996

show abstract

“…7,8 In an animal model, Faas et al 9 demonstrated that infusion of low-dose LPS induces a pre-eclampsia-like syndrome, including hypertension, proteinuria and glomerular endotheliosis. Lipolysaccharide leads to release of pro-inflammatory cytokines through activation of two major pattern recognition receptors present on innate immune cells, including the extracellular Toll-like receptor 2 (TLR2) and TLR4, 10 and the intracellular cryopyrin, a nucleotide-binding oligomerisation domain protein, also known as the caspase-activating recruitment domain. [11][12][13] Cryopyrin modulates LPSinduced caspase-1 activation and interleukin-1b (IL-1b) secretion.…”

Section: Introductionmentioning

confidence: 99%

Toll‐like receptors 2 and 4 and the cryopyrin inflammasome in normal pregnancy and pre‐eclampsia

Xie¹,

Hu²,

Turvey

et al. 2009

BJOG

View full text Add to dashboard Cite

Objective Pre-eclampsia involves a maternal inflammatory response that differs from both normal pregnancy and normotensive intrauterine growth restriction (IUGR). Our objective was to examine neutrophil Toll-like receptor (TLR), cryopyrin, nuclear factor-jB (NF-jB) subunit and interleukin-1b (IL-1b), and inflammatory cytokine profiles in women with preeclampsia or normotensive IUGR, as well as in normal pregnancy and non-pregnancy controls.Design and method A case-control study was performed. We examined the messenger RNA (mRNA) and protein expressions of TLR4 and TLR2, mRNA levels of cryopyrin, IL-1b, NF-jB subunits p50 and p65, as well as maternal serum inflammatory cytokine profiles (IL-2, IL-6, tumour necrosis factor-a [TNF-a], interferon-c [IFN-c] and IL-10) in women with and without pre-eclampsia using real-time reverse transcription polymerase chain reactions, flow cytometry and multiplex immunoassays.Setting A single tertiary maternity hospital in Vancouver, Canada.Population Women with early-onset pre-eclampsia (<34 weeks of gestation, n = 25), women with late-onset pre-eclampsia ( ‡34 +0 weeks of gestation, n = 25), women with normotensive IUGR (n = 25), women with normal pregnancy (n = 75) and non-pregnancy (n = 25) controls.Results Women with pre-eclampsia (as a single combined group of early-and late-onset, and particularly in women with earlyonset pre-eclampsia) had increased TLR2 and TLR4 mRNA and protein expressions elevated cryopyrin, NF-jB subunit, and IL-1b mRNA expression, and TNF-a:IL-10 and IL-6:IL-10 ratios compared with other groups.Conclusions These data suggest that TLRs and cryopyrin may modulate the innate immune response of the maternal syndrome of pre-eclampsia, and might also trigger the differential inflammatory response existing between early onset pre-eclampsia and normotensive IUGR.

show abstract

Cellular Recognition of Trimyristoylated Peptide or Enterobacterial Lipopolysaccharide via Both TLR2 and TLR4

Cited by 41 publications

References 61 publications

Campylobacter jejuni -Induced Activation of Dendritic Cells Involves Cooperative Signaling through Toll-Like Receptor 4 (TLR4)-MyD88 and TLR4-TRIF Axes

Campylobacter jejuni -Induced Activation of Dendritic Cells Involves Cooperative Signaling through Toll-Like Receptor 4 (TLR4)-MyD88 and TLR4-TRIF Axes

Toll-like receptor signaling in hen ovarian granulosa cells is dependent on stage of follicle maturation

Toll‐like receptors 2 and 4 and the cryopyrin inflammasome in normal pregnancy and pre‐eclampsia

Contact Info

Product

Resources

About