The mannose receptor mediates uptake of soluble but not of cell-associated antigen for cross-presentation.

Institute of Molecular Medicine and Experimental Immunology (IMMEI), Friedrich-Wilhelms-Universität, Bonn, Germany.
The Journal of Immunology (Impact Factor: 5.36). 07/2006; 176(11):6770-6. DOI: 10.4049/jimmunol.176.11.6770
Source: PubMed

ABSTRACT The mannose receptor (MR) has been implicated in the recognition and clearance of microorganisms and serum glycoproteins. Its endocytic function has been studied extensively using macrophages, although it is expressed by a variety of cell types, including dendritic cells (DC). In this study, we investigated its role in Ag presentation by DC using MR-/- mice. Uptake of the model Ag, soluble OVA, by bone marrow-derived DC and in vitro activation of OVA-specific CD8 T cells (OT-I cells) strictly depended on the MR. In vivo, MR deficiency impaired endocytosis of soluble OVA by DC and concomitant OT-I cell activation. No alterations in the DC subtype composition in MR-/- mice were accountable. Uptake of cell-associated OVA was unaffected by MR deficiency, resulting in unchanged activation of OT-I cells. These findings demonstrate that DC use the MR for endocytosis of a particular Ag type intended for cross-presentation.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: jimmun published online 31 October 2014 J Immunol Material Supplementary 8.DCSupplemental.html Subscriptions is online at: The Journal of Immunology Information about subscribing to Permissions http: Tolerance induction by dendritic cells (DCs) is, in part, mediated by the activation of regulatory T cells (Tregs). We have previously shown in vitro that human DCs treated with glucocorticoids (GCs), IL-10, or TGF-b upregulate the GC-Induced Leucine Zipper protein (GILZ). GILZ overexpression promotes DC differentiation into regulatory cells that generate IL-10– producing Ag-specific Tregs. To investigate whether these observations extend in vivo, we have generated CD11c-GILZ hi trans-genic mice. DCs from these mice constitutively overexpress GILZ to levels observed in GC-treated wild-type DCs. In this article, we establish that GILZ hi DCs display an accumulation of Foxp3 + Tregs in the spleens of young CD11c-GILZ hi mice. In addition, we show that GILZ hi DCs strongly increase the Treg pool in central and peripheral lymphoid organs of aged animals. Upon adoptive transfer to wild-type recipient mice, OVA-loaded GILZ hi bone marrow–derived DCs induce a reduced activation and proliferation of OVA-specific T cells as compared with control bone marrow–derived DCs, associated with an expansion of thymus-derived CD25 + Foxp3 + CD4 T cells. Transferred OVA-loaded GILZ hi DCs produce significantly higher levels of IL-10 and express reduced levels of MHC class II molecules as compared with OVA-loaded control DCs, emphasizing the regulatory phenotype of GILZ hi DCs in vivo. Thus, our work demonstrates in vivo that the GILZ overexpression alone is sufficient to promote a tolerogenic mode of function in DCs.
    The Journal of Immunology 10/2014; 193(12):0-0. DOI:10.4049/jimmunol.1400758 · 5.36 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Dendritic cells (DCs) are outstanding antigen presenting cells (APCs) due to their robust ability to internalize extracellular antigens using endocytic processes such as receptor-mediated endocytosis, phagocytosis, and macropinocytosis. Macropinocytosis mediates the non-specific uptake of soluble antigens and occurs in DCs constitutively. Macropinocytosis plays a key role in DC-mediated antigen presentation to T cells against pathogens and the efficiency of macropinocytosis in antigen capture is regulated during the process of DC maturation. Here, we review the methods to study macropinocytosis, describe our current knowledge of the regulatory mechanisms of antigen uptake via macropinocytosis and the intracellular trafficking route followed by macropinocytosed antigens, and discuss the significance of macropinocytosis for DC function.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Polysaccharides such as α- and β-glucans, chitin, and glycoproteins extensively modified with both N- and O-linked carbohydrates are the major components of fungal surfaces. The fungal cell wall is an excellent target for the action of antifungal agents, since most of its components are absent from mammalian cells. Recognition of these carbohydrate-containing molecules by the innate immune system triggers inflammatory responses and activation of microbicidal mechanisms by leukocytes. This review will discuss the structure of surface fungal glycoconjugates and polysaccharides and their recognition by innate immune receptors.
    Frontiers in Cellular and Infection Microbiology 10/2014; 4:145. DOI:10.3389/fcimb.2014.00145 · 2.62 Impact Factor


1 Download
Available from