Cell type-specific function of TRAF2 and TRAF3 in regulating type I IFN induction

Xie, Xiaoping; Jin, Jin; Zhu, Lele; Jie, Zuliang; Li, Yanchuan; Zhao, Baoyu; Cheng, Xuhong; Li, Pingwei; Sun, Shao‐Cong

doi:10.1186/s13578-018-0268-5

Cited by 21 publications

(12 citation statements)

References 28 publications

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“…The induction of IFN-I elicits the activation of the antiviral cellular gene expression that coincides with the inhibition of viral replication. The key role of TRAF3 in promoting antiviral signaling is supported by a recent study demonstrating that the deletion of TRAF3 in adult mice attenuated their host defense against vesicular stomatitis virus (VSV) infection (Xie et al, 2019). In the non-canonical NF-κB pathway, TRAF3, in concert with TRAF2, cIAP1 and cIAP2, promotes the constitutive degradation of NIK that in turn serves as negative regulator of IFN (Jin et al, 2014; Parvatiyar et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

TRAF3 Is Required for NF-κB Pathway Activation Mediated by HTLV Tax Proteins

et al. 2019

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Human T-cell leukemia viruses type 1 (HTLV-1) and type 2 (HTLV-2) share a common genome organization and expression strategy but have distinct pathological properties. HTLV-1 is the etiological agent of Adult T-cell Leukemia (ATL) and of HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP), whereas HTLV-2 does not cause hematological disorders and is only sporadically associated with cases of subacute myelopathy. Both HTLV genomes encode two regulatory proteins that play a pivotal role in pathogenesis: the transactivating Tax-1 and Tax-2 proteins and the antisense proteins HBZ and APH-2, respectively. We recently reported that Tax-1 and Tax-2 form complexes with the TNF-receptor associated factor 3, TRAF3, a negative regulator of the non-canonical NF-κB pathway. The NF-κB pathway is constitutively activated by the Tax proteins, whereas it is inhibited by HBZ and APH-2. The antagonistic effects of Tax and antisense proteins on NF-κB activation have not yet been fully clarified. Here, we investigated the effect of TRAF3 interaction with HTLV regulatory proteins and in particular its consequence on the subcellular distribution of the effector p65/RelA protein. We demonstrated that Tax-1 and Tax-2 efficiency on NF-κB activation is impaired in TRAF3 deficient cells obtained by CRISPR/Cas9 editing. We also found that APH-2 is more effective than HBZ in preventing Tax-dependent NF-κB activation. We further observed that TRAF3 co-localizes with Tax-2 and APH-2 in cytoplasmic complexes together with NF-κB essential modulator NEMO and TAB2, differently from HBZ and TRAF3. These results contribute to untangle the mechanism of NF-κB inhibition by HBZ and APH-2, highlighting the different role of the HTLV-1 and HTLV-2 regulatory proteins in the NF-κB activation.

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Section: Discussionmentioning

confidence: 99%

TRAF3 Is Required for NF-κB Pathway Activation Mediated by HTLV Tax Proteins

et al. 2019

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“…Therefore, in the present study, LPS and VSV treatment increased the effects of Ets2 on the TLR-mediated activation of the MyD88-MAPK/NF-κB pathway, which provides broader evidence of Ets2 in regulating inflammation via a mechanism similar to that of TLR 4 and 7. However, it should also be noted that VSV stimulation may also be MyD88-independent, which alternatively acts via TRAF2 and TRAF3 to induce type I interferon and antiviral immunity [25, 26]. Therefore, further studies are needed to investigate the possible role of Ets2 in the MyD88-independent mechanism of inflammatory regulation.…”

Section: Discussionmentioning

confidence: 99%

Ets2 suppresses inflammatory cytokines through MAPK/NF-κB signaling and directly binds to the IL-6 promoter in macrophages

Jiang

et al. 2019

Aging

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Proper activation of Toll-like receptor (TLR)-mediated signaling and production of proinflammatory cytokines are critical for the initiation of innate immunity, while the specific mechanism maintaining inflammatory homeostasis remains mostly unknown. Here, we show that Ets2 is upregulated following LPS and VSV stimulation. Ets2 knockdown or knockout leads to increased IL-6, TNF-α, and IFN-β production in macrophages. Consistently, Ets2-deficient mice show exacerbated inflammatory cytokine production and are more susceptible to CLP-induced sepsis. Mechanistically, Ets2 inhibits the LPS- and VSV-induced activation of ERK1/2, JNK, p38, and p65. Ets2 also binds to the promoter of IL-6 to inhibit transcription. Collectively, the results of the present study show the negative regulatory role of Ets2 in LPS- and VSV-induced inflammation through the suppression of MAPK/NF-κB signaling, direct binding to the IL-6 promoter and inhibition of transcription.

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“…Following the tubercle bacilli entering the cell, released Rv1988 localizes with the chromatin in the host nucleus affecting the expression of genes, which are important for host defense, e.g., NOX1, NOX4, NOS2 and TRAF3 [ 18 ]. The first three ones are an important source of reactive oxygen species [ 20 , 21 ] and the last one, together with TRAF2, plays a pivotal role in cell type—and stimulus-specific production of type I IFN [ 22 , 23 , 24 ]. Interesting observations have been made on another secretory mycobacterial protein, namely Rv2966c.…”

Section: Mycobacterium Tuberculosismentioning

confidence: 99%

Host Epigenetics in Intracellular Pathogen Infections

Fol

Włodarczyk

Druszczyńska

2020

IJMS

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Some intracellular pathogens are able to avoid the defense mechanisms contributing to host epigenetic modifications. These changes trigger alterations tothe chromatin structure and on the transcriptional level of genes involved in the pathogenesis of many bacterial diseases. In this way, pathogens manipulate the host cell for their own survival. The better understanding of epigenetic consequences in bacterial infection may open the door for designing new vaccine approaches and therapeutic implications. This article characterizes selected intracellular bacterial pathogens, including Mycobacterium spp., Listeria spp., Chlamydia spp., Mycoplasma spp., Rickettsia spp., Legionella spp. and Yersinia spp., which can modulate and reprogram of defense genes in host innate immune cells.

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Cell type-specific function of TRAF2 and TRAF3 in regulating type I IFN induction

Cited by 21 publications

References 28 publications

TRAF3 Is Required for NF-κB Pathway Activation Mediated by HTLV Tax Proteins

TRAF3 Is Required for NF-κB Pathway Activation Mediated by HTLV Tax Proteins

Ets2 suppresses inflammatory cytokines through MAPK/NF-κB signaling and directly binds to the IL-6 promoter in macrophages

Host Epigenetics in Intracellular Pathogen Infections

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