DEC-205 is a cell surface receptor for CpG oligonucleotides

Caminschi, Irina; Meuter, Simone; Heath, William R.

doi:10.4161/onci.23128

Cited by 11 publications

(18 citation statements)

References 10 publications

(12 reference statements)

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“…Here we show that, in the absence of any antigenic stimuli in vivo, liver Trm cell formation is increased by the presence of inflammatory signals generated by poly(I:C) or CpG adjuvants, with CpG B-P having a moderately greater effect than the other adjuvants. Use of CpG B-P was based on the observation that DEC205 contributes to the uptake of B class CpG ODN by dendritic cells, improving their potency (Caminschi et al, 2013), whereas P class CpG ODNs do not bind DEC205 (unpublished data). Because P class ODNs more efficiently trigger production of type I IFN, IL-6, and the CXCR3 ligand CXCL10 (Samulowitz et al, 2010), we fused a DEC205-binding B class ODN to a P class ODN to form a CpG B-P ODN that would bind DEC205 to facilitate uptake by dendritic cells and then utilize the superior cytokine-inducing properties of the P class ODN.…”

Section: Discussionmentioning

confidence: 99%

CD8+ T Cell Activation Leads to Constitutive Formation of Liver Tissue-Resident Memory T Cells that Seed a Large and Flexible Niche in the Liver

et al. 2018

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Graphical Abstract Highlights d TCR stimulation is essential for liver Trm cell formation d Liver Trm cells require IL-15 d Local antigen presentation and inflammation enhance liver Trm cell formation d Newly formed liver Trm cells do not displace existing Trm cell populations SUMMARY Liver tissue-resident memory T (Trm) cells migrate throughout the sinusoids and are capable of protecting against malaria sporozoite challenge. To gain an understanding of liver Trm cell development, we examined various conditions for their formation.Although liver Trm cells were found in naive mice, their presence was dictated by antigen specificity and required IL-15. Liver Trm cells also formed after adoptive transfer of in vitro-activated but not naive CD8 + T cells, indicating that activation was essential but that antigen presentation within the liver was not obligatory. These Trm cells patrolled the liver sinusoids with a half-life of 36 days and occupied a large niche that could be added to sequentially without effect on subsequent Trm cell cohorts. Together, our findings indicate that liver Trm cells form as a normal consequence of CD8 + T cell activation during essentially any infection but that inflammatory and antigenic signals preferentially tailor their development.

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Section: Discussionmentioning

confidence: 99%

CD8+ T Cell Activation Leads to Constitutive Formation of Liver Tissue-Resident Memory T Cells that Seed a Large and Flexible Niche in the Liver

et al. 2018

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“…The uptake of physiological TLR7/9 ligands and their shuttling to the endosomal compartment is a controlled, receptor-mediated process. However, detailed mechanisms of TLR7/9 ligand uptake are currently unclear and require further investigation (4).…”

Section: S1pr4 Signaling Attenuates Ilt 7 Internalization To Limit Ifmentioning

confidence: 99%

S1PR4 Signaling Attenuates ILT 7 Internalization To Limit IFN-α Production by Human Plasmacytoid Dendritic Cells

Dillmann

Ringel

Ringleb

et al. 2016

The Journal of Immunology

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Plasmacytoid dendritic cells (pDCs) produce large amounts of type I IFN in response to TLR7/9 ligands. This conveys antiviral effects, activates other immune cells (NK cells, conventional DCs, B, and T cells), and causes the induction and expansion of a strong inflammatory response. pDCs are key players in various type I IFN-driven autoimmune diseases such as systemic lupus erythematosus or psoriasis, but pDCs are also involved in (anti-)tumor immunity. The sphingolipid sphingosine-1-phosphate (S1P) signals through five G-protein-coupled receptors (S1PR1-5) to regulate, among other activities, immune cell migration and activation. The present study shows that S1P stimulation of human, primary pDCs substantially decreases IFN-α production after TLR7/9 activation with different types of CpG oligodeoxynucleotides or tick-borne encephalitis vaccine, which occurred in an S1PR4-dependent manner. Mechanistically, S1PR4 activation preserves the surface expression of the human pDC-specific inhibitory receptor Ig-like transcript 7. We provide novel information that Ig-like transcript 7 is rapidly internalized upon receptor-mediated endocytosis of TLR7/9 ligands to allow high IFN-α production. This is antagonized by S1PR4 signaling, thus decreasing TLR-induced IFN-α secretion. At a functional level, attenuated IFN-α production failed to alter Ag-driven T cell proliferation in pDC-dependent T cell activation assays, but shifted cytokine production of T cells from a Th1 (IFN-γ) to a regulatory (IL-10) profile. In conclusion, S1PR4 agonists block human pDC activation and may therefore be a promising tool to restrict pathogenic IFN-α production.

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“…Since TLR9 is localized within the endosomes and lysosomes of DCs, CpG DNA must be internalized prior to binding. CpG ODNs bind to DEC205 and mannose receptors to trigger TLR9-dependent responses ( Lahoud et al, 2012 ; Caminschi et al, 2013 ; Moseman et al, 2013 ). Granulin, HMGB1, LL-37, and β-defensin also facilitate incorporation of CpG ODNs ( Park et al, 2011 ; Ivanov et al, 2007 ; Hurtado and Peh, 2010 ; Tewary et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

CXCL14 Acts as a Specific Carrier of CpG DNA into Dendritic Cells and Activates Toll-like Receptor 9-mediated Adaptive Immunity

et al. 2017

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CXCL14 is a primordial chemokine that plays multiple roles in tumor suppression, autoimmune arthritis, and obesity-associated insulin resistance. However, the underlying molecular mechanisms are unclear. Here, we show that CXCL14 transports various types of CpG oligodeoxynucleotide (ODN) into the endosomes and lysosomes of bone marrow-derived dendritic cells (DCs), thereby activating Toll-like receptor 9 (TLR9). A combination of CpG ODN (ODN2395) plus CXCL14 induced robust production of IL-12 p40 by wild-type, but not Tlr9-knockout, DCs. Consistent with this, ODN2395-mediated activation of DCs was significantly attenuated in Cxcl14-knockout mice. CXCL14 bound CpG ODN with high affinity at pH 7.5, but not at pH 6.0, thereby enabling efficient delivery of CpG ODN to TLR9 in the endosome/lysosome. Furthermore, the CXCL14-CpG ODN complex specifically bound to high affinity CXCL14 receptors on DCs. Thus, CXCL14 serves as a specific carrier of CpG DNA to sensitize TLR9-mediated immunosurveillance.

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DEC-205 is a cell surface receptor for CpG oligonucleotides

Cited by 11 publications

References 10 publications

CD8+ T Cell Activation Leads to Constitutive Formation of Liver Tissue-Resident Memory T Cells that Seed a Large and Flexible Niche in the Liver

CD8+ T Cell Activation Leads to Constitutive Formation of Liver Tissue-Resident Memory T Cells that Seed a Large and Flexible Niche in the Liver

S1PR4 Signaling Attenuates ILT 7 Internalization To Limit IFN-α Production by Human Plasmacytoid Dendritic Cells

CXCL14 Acts as a Specific Carrier of CpG DNA into Dendritic Cells and Activates Toll-like Receptor 9-mediated Adaptive Immunity

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