TLR5 expression in the small intestine depends on the adaptors MyD88 and TRIF, but is independent of the enteric microbiota

Brandão, Inês; Hörmann, Nives; Jäckel, Sven; Reinhardt, Carsten

doi:10.1080/19490976.2015.1034417

Cited by 12 publications

(15 citation statements)

References 21 publications

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“…In a similar fashion, TRIF is recruited directly by TLR3 but is indirectly recruited to TLR4 via the bridging adaptor TRAM [4,[19][20][21]. In addition to MyD88, TLR5 responses are regulated by TRIF [22,23]. TLR4 is the only receptor that uses TRIF, TRAM, MyD88, and MAL, and thus, it serves as a prototype for both the TRIF-and MyD88-dependent pathways [24][25][26][27][28] (Fig.…”

Section: Introductionmentioning

confidence: 97%

TRIF-dependent TLR signaling, its functions in host defense and inflammation, and its potential as a therapeutic target

Ullah

Sweet

Mansell

et al. 2016

Journal of Leukocyte Biology

167

108

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Toll/IL-1R domain-containing adaptor-inducing IFN-β (TRIF)-dependent signaling is required for TLR-mediated production of type-I IFN and several other proinflammatory mediators. Various pathogens target the signaling molecules and transcriptional regulators acting in the TRIF pathway, thus demonstrating the importance of this pathway in host defense. Indeed, the TRIF pathway contributes to control of both viral and bacterial pathogens through promotion of inflammatory mediators and activation of antimicrobial responses. TRIF signaling also has both protective and pathologic roles in several chronic inflammatory disease conditions, as well as an essential function in wound-repair processes. Here, we review our current understanding of the regulatory mechanisms that control TRIF-dependent TLR signaling, the role of the TRIF pathway in different infectious and noninfectious pathologic states, and the potential for manipulating TRIF-dependent TLR signaling for therapeutic benefit.

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Section: Introductionmentioning

confidence: 97%

TRIF-dependent TLR signaling, its functions in host defense and inflammation, and its potential as a therapeutic target

Ullah

Sweet

Mansell

et al. 2016

Journal of Leukocyte Biology

167

108

View full text Add to dashboard Cite

show abstract

“…In addition to such secretory molecules, the regulation of TLR and TLR-related signaling molecule expression is reported as another mechanism by which IECs prevent excessive inflammation[ 14 – 17 ]. Notably, the regulation is bidirectional, and expression of these molecules is in turn partially regulated by gut microbiota; for example, TLR-MyD88-dependent expression of specific TLRs is differently affected by gut microbiota[ 18 , 19 ]. In this study, we focused on Toll-interacting protein (Tollip)[ 20 ], an inhibitor of TLRs and IL-1 family cytokine-related intracellular signaling, in IECs.…”

Section: Introductionmentioning

confidence: 99%

Post-Transcriptional Regulation of Toll-Interacting Protein in the Intestinal Epithelium

et al. 2016

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Immune responses against gut microbiota should be minimized to avoid unnecessary inflammation at mucosal surface. In this study, we analyzed the expression patterns of Toll-interacting protein (Tollip), an inhibitor of TLRs and IL-1 family cytokine-related intracellular signaling, in intestinal epithelial cells (IECs). Comparable mRNA expression was observed in murine small and large IECs (S-IECs and L-IECs). However, Tollip protein was only detected in L-IECs, but not in S-IECs. Similar results were obtained in germ-free mice, indicating that L-IEC-specific TOLLIP expression does not depend on bacterial colonization. Next, to understand the mechanisms underlying the post-transcriptional repression of Tollip, 3´-UTR-mediated translational regulation was evaluated. The region +1876/+2398 was responsible for the repression of Tollip expression. This region included the target sequence of miR-31. The inhibition of miR-31 restored the 3´-UTR-meditaed translational repression. In addition, miR-31 expression was significantly higher in S-IECs than in L-IECs, suggesting that miR-31 represses the translation of Tollip mRNA in S-IECs. Collectively, we conclude that the translation of Tollip is inhibited in S-IECs, at least in part, by miR-31 to yield L-IEC-specific high-level expression of the Tollip protein, which may contribute to the maintenance of intestinal homeostasis.

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“…Moreover, as TLR5 uses MYD88 and TRIF in its signaling pathway (Brandao et al ., ; Funami et al ., ), higher expression levels of these adaptors could be explained by the upregulation of TLR5 under the effect of spermatozoa with high DF.…”

Section: Discussionmentioning

confidence: 98%

“…Although synergistic TLR stimulation may often boost the immune responses, the order and time of TLRs stimulation can affect magnitude of the immune responses (Tan et al ., ). Moreover, increase in TLRs has been reported in other organs, although their DAMPs are still unknown (Brandao et al ., #24; Frantz et al ., #126).…”

Section: Discussionmentioning

confidence: 99%

Human sperm DNA damage has an effect on immunological interaction between spermatozoa and fallopian tube

et al. 2019

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Background: Toll-like receptors play a crucial role in the immunological interaction between the spermatozoa and fallopian tube and contribute to the ovulation, sperm capacitation, fertilization, and pregnancy. Objectives: To investigate the expression of toll-like receptors and their adaptor molecules and cytokines under the effect of spermatozoa with high DNA fragmentation (high DF) in human fallopian tube cell line (OE-E6/E7) and compare to those in normal spermatozoa. Materials and methods: Fresh semen samples were obtained from 10 unexplained infertile males with high DF (more than 20%) and from 10 healthy donors with a DF less than 3%. After sperm preparation, samples were co-cultured with OE-E6/E7. Toll-like receptors, myeloid differentiation factor 88 (MyD88), TIR domain-containing adapter protein (TIRAP), TIR domain-containing adapter-inducing IFN-b (TRIF), TRIF-related adapter molecule as well as IL-6, IL-8, IFN-b, and TNFa mRNA expression were evaluated by quantitative real-time PCR. Protein levels of these cytokines and chemokines were measured using ELISA method. Results: TLR 1-6 mRNA expression in OE-E6/E7 was significantly higher under the effect of spermatozoa with high DF compared to the spermatozoa with low DF. Furthermore, significantly increased mRNA expression of MyD88, TIRAP, and TRIF was observed in the high DF group compared to the low DF group, except TRIF-related adapter molecule. Moreover, the expression of IL-6 and IL-8 in the high DF group was significantly higher than low DF group, although there was no significant difference in IFN-b and TNFa expression between the groups. Discussion and conclusion: Damage-associated molecular patterns from DNA damage activate TLR signaling pathway in human fallopian tubes and result in the upregulation of inflammatory cytokines and chemokines. This situation may provide pathologic environment for capacitation, fertilization, embryo development, and implantation in female reproductive tract and can be one of the mechanisms of infertility in men with high DF.

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TLR5 expression in the small intestine depends on the adaptors MyD88 and TRIF, but is independent of the enteric microbiota

Cited by 12 publications

References 21 publications

TRIF-dependent TLR signaling, its functions in host defense and inflammation, and its potential as a therapeutic target

TRIF-dependent TLR signaling, its functions in host defense and inflammation, and its potential as a therapeutic target

Post-Transcriptional Regulation of Toll-Interacting Protein in the Intestinal Epithelium

Human sperm DNA damage has an effect on immunological interaction between spermatozoa and fallopian tube

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