The Class A Scavenger Receptor, Macrophage Receptor with Collagenous Structure, Is the Major Phagocytic Receptor for <i>Clostridium sordellii</i> Expressed by Human Decidual Macrophages

Thelen, Tennille D.; Hao, Yibai; Medeiros, Alexandra I.; Curtis, Jeffrey L.; Serezani, C. Henrique; Kobzik, Lester; Harris, Lisa H.; Aronoff, David M.

doi:10.4049/jimmunol.1000989

Cited by 79 publications

(85 citation statements)

References 53 publications

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“…These ligands have been previously shown to block the binding of C. sordellii to the class A SR MARCO (SR-A6) and binding of acetylated low-density lipoprotein to murine SR-AI. 35,53 These polyanionic compounds may also interfere with binding of CD163 to its ligands, but so far, this has not been investigated. Alternatively, polyanions may bind to positively charged residues present in exosites on ADAMTS13 that mediate its binding to CD163, as has been shown for fucoidan (supplemental Figure 4).…”

Section: Discussionmentioning

confidence: 99%

“…To further evaluate whether SRs might be involved in uptake of ADAMTS13, macrophages were preincubated with fucoidan and poly-I, which have previously been shown to block the binding of Clostridium sordellii to the class A receptor macrophage receptor with collagenous structure (MARCO). [34][35][36][37] Poly-C was used as a control for these experiments. Macrophages were preincubated with fucoidan, poly-I, and poly-C for 20 minutes at 37°C before the addition of ADAMTS13-AF488.…”

Section: Polyanionic Ligands Block the Internalization Of Adamts13 Bymentioning

confidence: 99%

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The class I scavenger receptor CD163 promotes internalization of ADAMTS13 by macrophages

et al. 2017

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Key Points• Uptake of ADAMTS13 by macrophages is not dependent on the macrophage mannose receptor.• CD163 promotes internalization of ADAMTS13 by macrophages.Internalization of ADAMTS13 by macrophages may contribute to its clearance from the circulation. Here we investigated endocytic mechanisms that contribute to the uptake of ADAMTS13 by macrophages. Human monocyte-derived macrophages were used to monitor the uptake of fluorescently labeled recombinant ADAMTS13 by flow cytometry.Internalization of ADAMTS13 was blocked upon addition of the cell-permeable dynamin inhibitor dynasore. Partial blocking of ADAMTS13 uptake was observed by using mannan;however, uptake was not affected by an antibody that blocked binding to the macrophage mannose receptor CD206, which suggests that other endocytic receptors contribute to the internalization of ADAMTS13 by macrophages. A pull-down with ADAMTS13 and subsequent mass spectrometric analysis identified the class I scavenger receptor CD163 as a candidate receptor for ADAMTS13. Blocking experiments with monoclonal anti-CD163 antibody EDHu-1 resulted in decreased ADAMTS13 internalization by macrophages. Pronounced inhibition of ADAMTS13 uptake by EDHu-1 was observed in CD163 high-expressing macrophages. In agreement with these findings, CD163-expressing Chinese hamster ovary cells were capable of rapidly internalizing ADAMTS13. Surface plasmon resonance revealed binding of ADAMTS13 to scavenger receptor cysteine-rich domains 1-9 and 1-5 of CD163. Taken together, our data identify CD163 as a major endocytic receptor for ADAMTS13 on macrophages.

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Section: Discussionmentioning

confidence: 99%

Section: Polyanionic Ligands Block the Internalization Of Adamts13 Bymentioning

confidence: 99%

The class I scavenger receptor CD163 promotes internalization of ADAMTS13 by macrophages

et al. 2017

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“…Given that phagocytosis is a critical innate mechanism that macrophages employ to eliminate invading spirochetes (28), we focused on the role of OspC in macrophage phagocytosis using a fluorometry-based method which allows quantification of fluorescence of internalized microorganisms in macrophages (48,65,66). We found that the ospC mutant had approximately 75% higher phagocytosis by murine PMs than the wild-type and the ospC-complemented strains (Fig.…”

Section: Fig 3 the Ospc Mutant Disseminates And Colonizes F4/80mentioning

confidence: 99%

Outer Surface Protein OspC Is an Antiphagocytic Factor That Protects Borrelia burgdorferi from Phagocytosis by Macrophages

et al. 2015

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cOuter surface protein C (OspC) is one of the major lipoproteins expressed on the surface of Borrelia burgdorferi during tick feeding and the early phase of mammalian infection. OspC is required for B. burgdorferi to establish infection in both immunocompetent and SCID mice and has been proposed to facilitate evasion of innate immune defenses. However, the exact biological function of OspC remains elusive. In this study, we showed that the ospC-deficient spirochete could not establish infection in NOD-scid IL2r␥ null mice that lack B cells, T cells, NK cells, and lytic complement. The ospC mutant also could not establish infection in anti-Ly6G-treated SCID and C3H/HeN mice (depletion of neutrophils). However, depletion of mononuclear phagocytes at the skin site of inoculation in SCID and C3H/HeN mice allowed the ospC mutant to establish infection in vivo. In phagocyte-depleted mice, the ospC mutant was able to colonize the joints and triggered neutrophilia during dissemination. Furthermore, we found that phagocytosis of green fluorescent protein (GFP)-expressing ospC mutant spirochetes by murine peritoneal macrophages and human THP-1 macrophage-like cells, but not in PMN-HL60, was significantly higher than parental wild-type B. burgdorferi strains, suggesting that OspC has an antiphagocytic property. In addition, overproduction of OspC in spirochetes also decreased the uptake of spirochetes by murine peritoneal macrophages. Together, our findings provide evidence that mononuclear phagocytes play a key role in clearance of the ospC mutant and that OspC promotes spirochetes' evasion of macrophages during early Lyme borreliosis. L yme disease, the most prevalent vector-borne illness in the United States (1), is a multisystem inflammatory disorder caused by infection with the spirochete Borrelia burgdorferi (2, 3). This spirochete is maintained in nature through a complex enzootic cycle involving Ixodes ticks and various small-mammal hosts. Humans, as accidental hosts, become infected after B. burgdorferiinfected ticks feed on them (4). Spirochetes replicate in the skin, spread locally, and induce an inflammatory response with a symptom known as erythema migrans, observed in most patients (2, 4). During disseminated infection, B. burgdorferi colonizes multiple tissues, leading to different clinical manifestations, including arthritis, myocarditis, and neurological and/or cutaneous abnormalities (2, 4). This acute, disseminated stage of human Lyme disease is largely recapitulated using inbred mouse strains which are susceptible to B. burgdorferi infection and develop carditis and subacute arthritis (5). Thus, the murine model provides a powerful tool to elucidate the role of spirochete virulence factors and host immunological responses during Lyme disease pathogenesis (4).The B. burgdorferi genome encodes a large number of surface lipoproteins, many of which are expressed during mammalian infection (4, 6, 7). One of these lipoproteins is the major outer surface protein C (OspC), whose production is induced within inf...

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“…To investigate the role of PpiA in phagocytosis of S. mutans by macrophages, we focused on class A SRs, SR-A and MARCO, which are suggested to function as phagocytic receptors for a variety of Gram-positive and -negative bacteria (7,26,34,48). After 45 min of stimulation with the wild-type 109c strain or the ppiA mutant of S. mutans, RNA from human macrophages was prepared, and mRNA levels of MARCO and SR-A were measured by quantitative RT-PCR (Fig.…”

Section: Localization Of Ppia On S Mutans Cellsmentioning

confidence: 99%

“…Of these SRs, the class A receptors, including scavenger receptor A (SR-A) and macrophage receptor with collagenous structure (MARCO), have been well characterized. These SR molecules are primarily expressed on macrophages, where they act as phagocytic receptors that mediate phagocytosis of pathogenic bacteria (27), such as S. pneumoniae, Staphylococcus aureus, Neisseria meningitidis, Clostridium sordellii, and Escherichia coli (7,26,34,48,54). Although it has been reported that lipopolysaccharide (LPS) and lipoteichoic acid (LTA) on the bacterial surface are ligands of the SRs (4,25), recent research suggests that bacterial surface proteins are major ligands for many SRs (5,18,33,37) and play a more important role as target molecules for SRs than do LPS and LTA.…”

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confidence: 99%

Surface Lipoprotein PpiA of Streptococcus mutans Suppresses Scavenger Receptor MARCO-Dependent Phagocytosis by Macrophages

et al. 2011

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Streptococcus mutans is associated with the initiation and progression of human dental caries and is occasionally isolated from the blood of patients with bacteremia and infective endocarditis. For the pathogen to survive in the infected host, surface lipoproteins of S. mutans are likely to play important roles in interactions with the innate immune system. To clarify the role that a putative lipoprotein, peptidyl-prolyl cis/transisomerase (PpiA), of S. mutans plays in the macrophage response, we investigated the response of THP-1-derived macrophages to S. mutans challenge. The deletion of the gene encoding Lgt eliminated PpiA on the cell surface of S. mutans, which implies that PpiA is a lipoprotein that is lipid anchored in the cell membrane by Lgt. Human and murine peritoneal macrophages both showed higher phagocytic activities for the ppiA and lgt mutants than the wild type, which indicates that the presence of PpiA reduces S. mutans phagocytosis. In addition, infection with S. mutans markedly induced mRNAs of macrophage receptor with collagenous structure (MARCO) and scavenger receptor A (SR-A) in human macrophages. In particular, transcriptional and translational levels of MARCO in human macrophages infected with the ppiA mutant were higher than those in macrophages infected with the wild type. Phagocytosis of S. mutans by human macrophages markedly decreased after treatment with anti-MARCO IgG. These results demonstrate that the S. mutans lipoprotein PpiA contributes to suppression of MARCO-mediated phagocytosis of this bacterium by macrophages.

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The Class A Scavenger Receptor, Macrophage Receptor with Collagenous Structure, Is the Major Phagocytic Receptor for Clostridium sordellii Expressed by Human Decidual Macrophages

Cited by 79 publications

References 53 publications

The class I scavenger receptor CD163 promotes internalization of ADAMTS13 by macrophages

The class I scavenger receptor CD163 promotes internalization of ADAMTS13 by macrophages

Outer Surface Protein OspC Is an Antiphagocytic Factor That Protects Borrelia burgdorferi from Phagocytosis by Macrophages

Surface Lipoprotein PpiA of Streptococcus mutans Suppresses Scavenger Receptor MARCO-Dependent Phagocytosis by Macrophages

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