Recognition of Bacterial Capsular Polysaccharides and Lipopolysaccharides by the Macrophage Mannose Receptor

Zamze, Susanne; Martı́nez-Pomares, Luisa; Jones, Hannah; Taylor, Philip Russel; Stillion, Richard J.; Gordon, Siamon; Wong, Siew Yee

doi:10.1074/jbc.m207057200

Cited by 195 publications

(171 citation statements)

References 57 publications

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“…P. aeruginosa slime-GLP, a strong TNF-a inducer, contains mannose, which is absent from the homologous LPS [26,27] and mediates the biological activities of P. aeruginosa slime-GLP [28]. Previous work by Zamze et al [41] demonstrated that P. aeruginosa LPS does not bind MR in vitro, whereas structurally irrelevant LPS from other bacteria do so, suggesting a way of recognition that does not rely on linear epitopes. In agreement with those studies, we herein observe that blocking MR did not exert any effect on TNF-a production through P. aeruginosa LPS, but almost abolished it by slime-GLP and viable P. aeruginosa bacteria.…”

Section: Discussionmentioning

confidence: 99%

Synergistic regulation of Pseudomonas aeruginosa‐induced cytokine production in human monocytes by mannose receptor and TLR2

et al. 2009

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The immune response to pathogen is regulated by a combination of specific PRR, which are involved in pathogen recognition. Pseudomonas aeruginosa, a bacterium that causes life-threatening disease in immuno-compromised host, is recognized by distinct members of the TLR family. We have previously shown that viable P. aeruginosa bacteria are recognized by human monocytes mainly through TLR2. Using ligand-specific blocking antibodies, we herein show that the mannose receptor (MR), a phagocytic receptor for unopsonized P. aeruginosa bacteria, contributes equally to TLR2 in proinflammatory cytokine production by human monocytes in response to P. aeruginosa infection. Synergy of both receptors totally controls the immune response. Viable P. aeruginosa bacteria activate NF-jB and MAPK pathways and enhance TLR2-mediated signaling in MR-transfected human embryonic kidney 293 cells. Moreover, MR follows the same kinetics and colocalizes with TLR2 in the endosome during in vivo infection of human macrophages with P. aeruginosa. The studies provide the first demonstration of a significant role for MR, synergistic with TLR2, in activating a proinflammatory response to P. aeruginosa infection.Key words: Mannose receptor . NF-kB . Pseudomonas aeruginosa . TLR . TNF-a IntroductionThe innate immune system relies on a vast array of non-clonally expressed PRR to detect pathogens. PRR bind conserved molecular structures known as PAMP, which are shared by a large group of pathogens. PRR binding to microbial products elicits a signaling response within leukocytes to produce immune modulators in a PRR-dependent manner [1]. Proinflammatory cytokine production by monocyte/macrophage lineage orchestrates the immune response and predicts the outcome of infection. The overall immune response depends on the combination of engaged PRR and their specific ligands. This complexity allows the immune system not only to tailor its response to a specific pathogen but also to discriminate the site of infection or the microbial burden.Host recognition of PAMP may result in two entirely different outcomes. An appropriate response leads to the eradication of a microorganism [2], but an exaggerated inflammatory response may lead to illnesses such as sepsis and shock [3]. TLR are the best-characterized signal-generating receptors among the PRR. They initiate key inflammatory responses and shape adaptive immunity [4]. All human TLR ($11) are type I transmembrane glycoproteins containing an extracellular domain with leucinerich repeats responsible for ligand recognition and a cytoplasmic Toll/IL-1 receptor homology domain required for initiating signaling [5]. Working as homo-or heterodimers alone or with other PRR, they recognize a diverse array of microbial components in bacteria, fungi, parasites, and viruses. This includes lipid-based bacterial cell wall components such as LPS and lipopeptides, microbial protein components such as flagellin and profilin-like molecules, and nucleic acids such as dsRNA, ssRNA, and CpG DNA [6].TLR participate with additio...

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Section: Discussionmentioning

confidence: 99%

Synergistic regulation of Pseudomonas aeruginosa‐induced cytokine production in human monocytes by mannose receptor and TLR2

et al. 2009

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“…They have been implicated in CNS inflammation and more recently in AD (21). To identify perivascular macrophages, we used CD163, a hemoglobinhaptoglobin scavenger receptor, and CD206, a mannose receptor (20,26,27). Analysis of SR-BI mutant mice revealed a remarkable increase in CD206 and CD163 in the brain.…”

Section: Discussionmentioning

confidence: 99%

“…To evaluate the impact of SR-BI reduction in perivascular macrophages in the mouse brain, we analyzed the expression of CD206 and CD163 in SR-BI +/− and −/− mice. CD206, a mannose receptor, and CD163, a scavenger receptor, have been identified as perivascular macrophage markers (26,27). Analysis of total protein brain extracts by Western blotting showed a significant increase in both CD206 and CD163 in SR-BI +/− and −/− mice compared with wild-type mice (n = 5) (CD206 wild-type versus SR-BI +/− , P = 0.0446; wild-type versus SR-BI −/− , P = 0.0018; CD163 wild-type versus SR-BI +/− , P = 0.0467; wild-type versus SR-BI −/− , P = 0.0064; Fig.…”

Section: Sr-bi Reduction Increases Perivascular Macrophages In the Mousementioning

confidence: 99%

Scavenger receptor class B type I (SR-BI) regulates perivascular macrophages and modifies amyloid pathology in an Alzheimer mouse model

Thanopoulou

Fragkouli

Stylianopoulou

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

128

114

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Scavenger receptor class B type I (SR-BI) is a high-density lipoprotein receptor that regulates cholesterol efflux from the peripheral tissues to the liver. SR-BI has been identified on astrocytes and vascular smooth muscle cells in Alzheimer's disease brain and has been shown to mediate adhesion of microglia to fibrillar amyloid-β (Aβ). Here we report that SR-BI mediates perivascular macrophage response and regulates Aβ-related pathology and cerebral amyloid angiopathy in an Alzheimer's mouse model. Reduction or deletion of SR-BI gene in heterozygous or homozygous deficient mice (SR-BI +/− , −/− ) resulted in a significant increase in perivascular macrophages in the brain. SR-BI deletion had no effect on apolipoprotein E or apolipoprotein AI levels in the mouse brain. Our analysis revealed increased levels of SR-BI expression in the brains of human amyloid precursor protein (Swedish, Indiana) transgenic mice (J20 line). To evaluate the role of SR-BI in Alzheimer's disease pathogenesis, we inactivated one SR-BI allele in J20 transgenic mice. SR-BI reduction in J20/SR-BI +/− mice enhanced fibrillar amyloid deposition and cerebral amyloid angiopathy and also exacerbated learning and memory deficits compared with J20 littermates. Immunohistochemical analysis revealed localization of SR-BI on perivascular macrophages in tight association with Aβ deposits. Our data suggest that SR-BI reduction impairs the response of perivascular macrophages to Aβ and enhances the Aβ-related phenotype and cerebral amyloid angiopathy in J20 mice. These results reveal that SR-BI, a scavenger receptor primarily involved in high-density lipoprotein cholesterol transport, plays an essential role in Alzheimer's disease and cerebral amyloid angiopathy.high-density lipoprotein receptor | dementia

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“…Cells were kept in serum-free medium (Opti-MEM; Invitrogen) after transfection, and supernatant was collected after 3 days. Purification of sMR-HA was performed by affinity chromatography using an anti-MR monoclonal antibody (clone MR5D3 purchased from HyCult blotachnology b.v.) conjugated to gammabind plus Sepharose as described (26).…”

Section: Expression and Purification Of A Hemaglutinin-tagged Solublementioning

confidence: 99%

Structural Model for the Mannose Receptor Family Uncovered by Electron Microscopy of Endo180 and the Mannose Receptor

Boskovic

Arnold

Stilion

et al. 2006

Journal of Biological Chemistry

Self Cite

107

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The mannose receptor family comprises four members in mammals, Endo180 (CD280), DEC-205 (CD205), phospholipase A 2 receptor (PLA 2 R) and the mannose receptor (MR, CD206), whose extracellular portion contains a similar domain arrangement: an N-terminal cysteine-rich domain (CysR) followed by a single fibronectin type II domain (FNII) and 8 -10 C-type lectin-like domains (CTLDs). These proteins mediate diverse functions ranging from extracellular matrix turnover through collagen uptake to homeostasis and immunity based on sugar recognition. Endo180 and the MR are multivalent transmembrane receptors capable of interacting with multiple ligands; in both receptors FNII recognizes collagens, and a single CTLD retains lectin activity (CTLD2 in Endo180 and CTLD4 in MR). It is expected that the overall conformation of these multivalent molecules would deeply influence their function as the availability of their binding sites could be altered under different conditions. However, conflicting reports have been published on the three-dimensional arrangement of these receptors. Here, we have used single particle electron microscopy to elucidate the three-dimensional organization of the MR and Endo180. Strikingly, we have found that both receptors display distinct threedimensional structures, which are, however, conceptually very similar: a bent and compact conformation built upon interactions of the CysR domain and the lone functional CTLD. Biochemical and electron microscopy experiments indicate that, under a low pH mimicking the endosomal environment, both MR and Endo180 experience large conformational changes. We propose a structural model for the mannose receptor family where at least two conformations exist that may serve to regulate differences in ligand selectivity.The mannose receptor (MR 4 and CD206), together with Endo180 (also known as the urokinase-type plasminogen activator receptor-associated protein (uPARAP) and CD280), the dendritic cell receptor DEC-205 (CD205) and the M-type phospholipase A 2 receptor (PLA 2 R) encompass the mannose receptor family of endocytic receptors (1, 2). The members of this family are unique within the superfamily of C-type lectins as these alone contain multiple C-type lectin-like domains (CTLDs) within a single polypeptide backbone. All these receptors are recycled between the plasma membrane and the endosomal apparatus and mediate the uptake of extracellular ligands for intracellular delivery (2). Recently, an avian structural homologue of the mammalian mannose receptor family members, FcRY, has been discovered to function as a yolk sac IgY receptor (3).The MR was originally described as a transmembrane receptor that recognized saccharide chains terminating in mannose and designated as the macrophage mannose receptor. Since its expression was found not to be restricted to macrophages, it is now known as MR (2). MR executes important roles in the immune system by functioning as a pattern recognition receptor toward a wide range of pathogens. Other members of the family were found ...

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Recognition of Bacterial Capsular Polysaccharides and Lipopolysaccharides by the Macrophage Mannose Receptor

Cited by 195 publications

References 57 publications

Synergistic regulation of Pseudomonas aeruginosa‐induced cytokine production in human monocytes by mannose receptor and TLR2

Synergistic regulation of Pseudomonas aeruginosa‐induced cytokine production in human monocytes by mannose receptor and TLR2

Scavenger receptor class B type I (SR-BI) regulates perivascular macrophages and modifies amyloid pathology in an Alzheimer mouse model

Structural Model for the Mannose Receptor Family Uncovered by Electron Microscopy of Endo180 and the Mannose Receptor

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