The mannose receptor: linking homeostasis and immunity through sugar recognition

Taylor, Philip Russel; Gordon, Siamon; Martı́nez-Pomares, Luisa

doi:10.1016/j.it.2004.12.001

Cited by 306 publications

(267 citation statements)

References 82 publications

(103 reference statements)

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“…In contrast to Siglecs, the binding of mannose receptors to exposed mannose residues results in cell activation and enhanced antigen presentation. 20 Glycosylation can, therefore, be a general mechanism for generating immune response while utilizing a limited set of receptor-ligand interactions.…”

Section: Healthy Cells Avert Immune Recognition By Virtue Of Their Nomentioning

confidence: 99%

Glycosylation: an intrinsic sign of "Danger"

Rachmilewitz¹

2010

Self/Nonself

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T he "danger" model of immunity posits that the immune system is triggered by endogenous danger signals, rather than exogenous non-self signals per se. It has been proposed that danger signals may consist of both intracellular "pre-packed" molecules released from damaged cells and stress-induced proteins. Here we focus on glycosylation aberrancies as a unifying concept for danger signaling. According to this proposition glycosylation patterns reliably reflect cellular phenotypic state and appearance of altered carbohydrate structures may constitute a pivotal phenotypic alteration that alarms the immune system to danger and initiates immunity. Viewed from this vantage point, healthy cells avert immune recognition by virtue of their normal terminal glycosylation patterns. By contrast, abnormal cells display and release glycoproteins and glycolipids with aberrant terminal glycosylation trees, which in turn immunologically flag these cells. Diverse carbohydrate-binding receptors are expressed on immune cells and are used to detect these phenotypic changes. Thus, in addition to the "pre-packed" and stress-induced signals this glycosylation-based signal represents an endogenous signal reliably reflecting the cell phenotypic status, enabling the immune system to monitor the tissue/ cell's physical condition and to respond accordingly.

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Section: Healthy Cells Avert Immune Recognition By Virtue Of Their Nomentioning

confidence: 99%

Glycosylation: an intrinsic sign of "Danger"

Rachmilewitz¹

2010

Self/Nonself

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“…Some of MR endogenous ligands are targeted by the immune system in the context of autoimmune diseases such as thyroglobulin in the case of thyroditis [26,32] and myeloperoxidase in the case of glomerulonephritis [33]. We previously hypothesised that inappropriate presentation of these ligands to the acquired immune system could be facilitated through their interaction with MR expressed by subpopulations of DC [12]. It is intriguing that collagens II and IV can also be targeted by the acquired system since collagen II, a major component of cartilage, is an important autoantigen in rheumatoid arthritis patients [34], and collagen IV contains the antigen recognised by autoantibodies from Goodpasture syndrome patients [35].…”

Section: Mr and Self Recognitionmentioning

confidence: 99%

“…This cytokine induces a deactivated anti-inflammatory state in the Mu and is a key player in the control of inflammation in vivo [6] One of the hallmarks of alternatively activated and deactivated MU is increased expression of the mannose receptor (MR, CD206) [1,7]. The MR was originally described as an endocytic receptor for lysosomal enzymes [8] and studies in MR-deficient mice support the idea that MR is primarily a homeostatic clearance system with an additional role as a pathogen receptor [9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Carbohydrate‐independent recognition of collagens by the macrophage mannose receptor

Martı́nez-Pomares¹,

Wienke

Stillion³

et al. 2006

Eur J Immunol

130

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Mannose receptor (MR) is the best characterised member of a family of four endocytic molecules that share a common domain structure; a cysteine-rich (CR) domain, a fibronectin-type II (FNII) domain and tandemly arranged C-type lectin-like domains (CTLD, eight in the case of MR). Two distinct lectin activities have been described for MR. The CR domain recognises sulphated carbohydrates while the CTLD mediate binding to mannose, fucose or N-acetylglucosamine. FNII domains are known to be important for collagen binding and this has been studied in the context of two members of the MR family, Endo180 and the phospholipase A 2 receptor. Here, we have investigated whether the broad and effective lectin activity mediated by the CR domain and CTLD of MR is favoured to the detriment of FNII-mediated interaction(s). We show that MR is able to bind and internalise collagen in a carbohydrate-independent manner and that MR deficient macrophages have a marked defect in collagen IV and gelatin internalisation. These data have major implications at the molecular level as there are now three distinct ligand-binding sites described for MR. Furthermore our findings extend the range of endogenous ligands recognised by MR, a molecule firmly placed at the interface between homeostasis and immunity.

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“…Primarily expressed by macrophages and dendritic cells, the mannose receptor is a type-1 membrane protein with eight tandemly arranged CRD domains. These allow the recognition of various carbohydrates terminating in L-fucose, D-mannose and N-acetyl glucosamine (Taylor, Gordon et al 2005). In addition to CRDs at the extracellular region, MR has two additional domains, an N-terminal cysteine-rich domain and a fibronectin II domain, these are involved in calcium-independent binding to sulphated sugars and collagen, respectively.…”

Section: C-type Lectin Receptors (Clrs)mentioning

confidence: 99%

“…In addition to CRDs at the extracellular region, MR has two additional domains, an N-terminal cysteine-rich domain and a fibronectin II domain, these are involved in calcium-independent binding to sulphated sugars and collagen, respectively. Unlike the CRDs, these additional domains are only involved in the recognition of endogenous ligands and not those of microbial origin (Taylor, Gordon et al 2005;Napper, Drickamer et al 2006). The role of the MR in host defence remains a mystery: animal knockout models do not demonstrate an increased susceptibility to pathogens such as Candida albicans and mycobacteria which are known to contain MR ligands (Wojcikiewicz, Zhang et al 2003;Appelmelk, den Dunnen et al 2008).…”

Section: C-type Lectin Receptors (Clrs)mentioning

confidence: 99%