Mannose receptor polyubiquitination regulates endosomal recruitment of p97 and cytosolic antigen translocation for cross-presentation

Zehner, Matthias; Chasan, Achmet Imam; Schuette, Verena; Embgenbroich, Maria; Quast, Thomas; Kolanus, Waldemar; Burgdorf, Sven

doi:10.1073/pnas.1102397108

Cited by 78 publications

(94 citation statements)

References 38 publications

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“…As such, DNGR-1 may be a useful subcellular marker for identifying and characterizing the elusive "cross-presentation compartment" in CD8α + DCs. Of course, our data do not exclude the possibility that DNGR-1 may additionally control the process of cross-presentation, for example, by promoting fusion with the ER-Golgi intermediate compartment (65) or by facilitating translocation of ligand to the cytosol, as recently shown for another myeloid CLR, the mannose receptor (66). Consistent with that notion, the Y7F hemITAM mutant DNGR-1 still localized to the recycling endosomal compartment even though it was impaired in its ability to promote cross-presentation of dead cell-associated antigens (unpublished observation).…”

Section: Discussionmentioning

confidence: 89%

The dendritic cell receptor DNGR-1 controls endocytic handling of necrotic cell antigens to favor cross-priming of CTLs in virus-infected mice

Zelenay¹,

Keller²,

Whitney³

et al. 2012

J. Clin. Invest.

229

227

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DNGR-1 (CLEC9A) is a receptor for necrotic cells required by DCs to cross-prime CTLs against dead cell antigens in mice. It is currently unknown how DNGR-1 couples dead cell recognition to cross-priming. Here we found that DNGR-1 did not mediate DC activation by dead cells but rather diverted necrotic cell cargo into a recycling endosomal compartment, favoring cross-presentation to CD8 + T cells. DNGR-1 regulated crosspriming in non-infectious settings such as immunization with antigen-bearing dead cells, as well as in highly immunogenic situations such as infection with herpes simplex virus type 1. Together, these results suggest that DNGR-1 is a dedicated receptor for cross-presentation of cell-associated antigens. Our work thus underscores the importance of cross-priming in immunity and indicates that antigenicity and adjuvanticity can be decoded by distinct innate immune receptors. The identification of specialized receptors that regulate antigenicity of virus-infected cells reveals determinants of antiviral immunity that might underlie the human response to infection and vaccination.

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Section: Discussionmentioning

confidence: 89%

The dendritic cell receptor DNGR-1 controls endocytic handling of necrotic cell antigens to favor cross-priming of CTLs in virus-infected mice

Zelenay¹,

Keller²,

Whitney³

et al. 2012

J. Clin. Invest.

229

227

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“…Low expression levels of CD206 by DC2.4 have also been confirmed by others. 39 Despite the popularity of the DC2.4…”

Section: Resultsmentioning

confidence: 99%

pH-Degradable Mannosylated Nanogels for Dendritic Cell Targeting

Coen¹,

Vanparijs

Risseeuw³

et al. 2016

Biomacromolecules

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We report on the design of glycosylated nanogels via core-cross-linking of amphiphilic non-watersoluble block copolymers composed of an acetylated glycosylated block and a pentafluorophenyl (PFP) activated ester block prepared by RAFT polymerization. Self-assembly, pH-sensitive corecross-linking and removal of remaining PFP esters and protecting groups is achieved in one-pot yielding fully hydrated sub-100 nm nanogels. Using cell subsets that exhibit high and low expression of the mannose receptor under conditions that suppress active endocytosis, we show that mannosylated but not galactosylated nanogels can efficiently target the mannose receptor (MR) that is expressed on the cell surface of primary dendritic cells (DCs). These nanogels hold promise for immunological applications involving DCs and macrophage subsets.

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“…It was suggested for mouse DCs that cross presentation of soluble ovalbumin internalized by MR, presumably targeted to early endosomes, is more efficient than cross presentation after fluid phase uptake, which also delivers an unspecified portion of soluble ovalbumin to late endosomes. [16][17][18] Early endosomes also may host the cross presentation of liposome-encapsulated hen egg lysozyme, but in a fashion independent of the proteasomal pathway. 19,20 Experiments where an antigen was coupled to DC-SIGN antibodies also suggested that early endosomal targeting may facilitate cross presentation by human DC-SIGN transgenic mouse DCs.…”

Section: Introductionmentioning

confidence: 99%

Internalization and endosomal degradation of receptor-bound antigens regulate the efficiency of cross presentation by human dendritic cells

Chatterjee

Smed‐Sörensen

Cohn³

et al. 2012

Blood

168

204

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Dendritic cells (DCs) can capture extracellular antigens and load resultant peptides on to MHC class I molecules, a process termed cross presentation. The mechanisms of cross presentation remain incompletely understood, particularly in primary human DCs. One unknown is the extent to which antigen delivery to distinct endocytic compartments determines cross presentation efficiency, possibly by influencing antigen egress to the cytosol. We addressed the problem directly and quantitatively by comparing the cross presentation of identical antigens conjugated with antibodies against different DC receptors that are targeted to early or late endosomes at distinct efficiencies. In human BDCA1 ؉ and monocyte-derived DCs, CD40 and mannose receptor targeted antibody conjugates to early endosomes, whereas DEC205 targeted antigen primarily to late compartments. Surprisingly, the receptor least efficient at internalization, CD40, was the most efficient at cross presentation. This did not reflect DC activation by CD40, but rather its relatively poor uptake or intraendosomal degradation compared with mannose receptor or DEC205. Thus, although both early and late endosomes appear to support cross presentation in human DCs, internalization efficiency, especially to late compartments, may be a negative predictor of activity when selecting receptors for vaccine development.

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Mannose receptor polyubiquitination regulates endosomal recruitment of p97 and cytosolic antigen translocation for cross-presentation

Cited by 78 publications

References 38 publications

The dendritic cell receptor DNGR-1 controls endocytic handling of necrotic cell antigens to favor cross-priming of CTLs in virus-infected mice

The dendritic cell receptor DNGR-1 controls endocytic handling of necrotic cell antigens to favor cross-priming of CTLs in virus-infected mice

pH-Degradable Mannosylated Nanogels for Dendritic Cell Targeting

Internalization and endosomal degradation of receptor-bound antigens regulate the efficiency of cross presentation by human dendritic cells

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