PubMed:12496255 JSONTXT

{"project":"GlyCosmos6-Glycan-Motif-Image","denotations":[{"id":"T1","span":{"begin":115,"end":122},"obj":"Glycan_Motif"},{"id":"T2","span":{"begin":519,"end":526},"obj":"Glycan_Motif"},{"id":"T3","span":{"begin":1753,"end":1760},"obj":"Glycan_Motif"},{"id":"T4","span":{"begin":2071,"end":2078},"obj":"Glycan_Motif"}],"attributes":[{"id":"A1","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G70323CJ"},{"id":"A2","pred":"image","subj":"T2","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G70323CJ"},{"id":"A3","pred":"image","subj":"T3","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G70323CJ"},{"id":"A4","pred":"image","subj":"T4","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G70323CJ"}],"text":"The cell surface receptor DC-SIGN discriminates between Mycobacterium species through selective recognition of the mannose caps on lipoarabinomannan.\nInteractions between dendritic cells (DCs) and Mycobacterium tuberculosis, the etiological agent of tuberculosis, most likely play a key role in anti-mycobacterial immunity. We have recently shown that M. tuberculosis binds to and infects DCs through ligation of the DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and that M. tuberculosis mannose-capped lipoarabinomannan (ManLAM) inhibits binding of the bacilli to the lectin, suggesting that ManLAM might be a key DC-SIGN ligand. In the present study, we investigated the molecular basis of DC-SIGN ligation by LAM. Contrary to what was found for slow growing mycobacteria, such as M. tuberculosis and the vaccine strain Mycobacterium bovis bacillus Calmette-Guérin, our data demonstrate that the fast growing saprophytic species Mycobacterium smegmatis hardly binds to DC-SIGN. Consistent with the former finding, we show that M. smegmatis-derived lipoarabinomannan, which is capped by phosphoinositide residues (PILAM), exhibits a limited ability to inhibit M. tuberculosis binding to DC-SIGN. Moreover, using enzymatically demannosylated and chemically deacylated ManLAM molecules, we demonstrate that both the acyl chains on the ManLAM mannosylphosphatidylinositol anchor and the mannooligosaccharide caps play a critical role in DC-SIGN-ManLAM interaction. Finally, we report that DC-SIGN binds poorly to the PILAM and uncapped AraLAM-containing species Mycobacterium fortuitum and Mycobacterium chelonae, respectively. Interestingly, smooth colony-forming Mycobacterium avium, in which ManLAM is capped with single mannose residues, was also poorly recognized by the lectin. Altogether, our results provide molecular insight into the mechanisms of mycobacteria-DC-SIGN interaction, and suggest that DC-SIGN may act as a pattern recognition receptor and discriminate between Mycobacterium species through selective recognition of the mannose caps on LAM molecules."}

{"project":"sentences","denotations":[{"id":"T1","span":{"begin":0,"end":149},"obj":"Sentence"},{"id":"T2","span":{"begin":150,"end":323},"obj":"Sentence"},{"id":"T3","span":{"begin":324,"end":661},"obj":"Sentence"},{"id":"T4","span":{"begin":662,"end":747},"obj":"Sentence"},{"id":"T5","span":{"begin":748,"end":1010},"obj":"Sentence"},{"id":"T6","span":{"begin":1011,"end":1227},"obj":"Sentence"},{"id":"T7","span":{"begin":1228,"end":1493},"obj":"Sentence"},{"id":"T8","span":{"begin":1494,"end":1656},"obj":"Sentence"},{"id":"T9","span":{"begin":1657,"end":1812},"obj":"Sentence"},{"id":"T10","span":{"begin":1813,"end":2101},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"The cell surface receptor DC-SIGN discriminates between Mycobacterium species through selective recognition of the mannose caps on lipoarabinomannan.\nInteractions between dendritic cells (DCs) and Mycobacterium tuberculosis, the etiological agent of tuberculosis, most likely play a key role in anti-mycobacterial immunity. We have recently shown that M. tuberculosis binds to and infects DCs through ligation of the DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and that M. tuberculosis mannose-capped lipoarabinomannan (ManLAM) inhibits binding of the bacilli to the lectin, suggesting that ManLAM might be a key DC-SIGN ligand. In the present study, we investigated the molecular basis of DC-SIGN ligation by LAM. Contrary to what was found for slow growing mycobacteria, such as M. tuberculosis and the vaccine strain Mycobacterium bovis bacillus Calmette-Guérin, our data demonstrate that the fast growing saprophytic species Mycobacterium smegmatis hardly binds to DC-SIGN. Consistent with the former finding, we show that M. smegmatis-derived lipoarabinomannan, which is capped by phosphoinositide residues (PILAM), exhibits a limited ability to inhibit M. tuberculosis binding to DC-SIGN. Moreover, using enzymatically demannosylated and chemically deacylated ManLAM molecules, we demonstrate that both the acyl chains on the ManLAM mannosylphosphatidylinositol anchor and the mannooligosaccharide caps play a critical role in DC-SIGN-ManLAM interaction. Finally, we report that DC-SIGN binds poorly to the PILAM and uncapped AraLAM-containing species Mycobacterium fortuitum and Mycobacterium chelonae, respectively. Interestingly, smooth colony-forming Mycobacterium avium, in which ManLAM is capped with single mannose residues, was also poorly recognized by the lectin. Altogether, our results provide molecular insight into the mechanisms of mycobacteria-DC-SIGN interaction, and suggest that DC-SIGN may act as a pattern recognition receptor and discriminate between Mycobacterium species through selective recognition of the mannose caps on LAM molecules."}

{"project":"GlyCosmos6-Glycan-Motif-Structure","denotations":[{"id":"T1","span":{"begin":115,"end":122},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T2","span":{"begin":519,"end":526},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T3","span":{"begin":1753,"end":1760},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T4","span":{"begin":2071,"end":2078},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"}],"text":"The cell surface receptor DC-SIGN discriminates between Mycobacterium species through selective recognition of the mannose caps on lipoarabinomannan.\nInteractions between dendritic cells (DCs) and Mycobacterium tuberculosis, the etiological agent of tuberculosis, most likely play a key role in anti-mycobacterial immunity. We have recently shown that M. tuberculosis binds to and infects DCs through ligation of the DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and that M. tuberculosis mannose-capped lipoarabinomannan (ManLAM) inhibits binding of the bacilli to the lectin, suggesting that ManLAM might be a key DC-SIGN ligand. In the present study, we investigated the molecular basis of DC-SIGN ligation by LAM. Contrary to what was found for slow growing mycobacteria, such as M. tuberculosis and the vaccine strain Mycobacterium bovis bacillus Calmette-Guérin, our data demonstrate that the fast growing saprophytic species Mycobacterium smegmatis hardly binds to DC-SIGN. Consistent with the former finding, we show that M. smegmatis-derived lipoarabinomannan, which is capped by phosphoinositide residues (PILAM), exhibits a limited ability to inhibit M. tuberculosis binding to DC-SIGN. Moreover, using enzymatically demannosylated and chemically deacylated ManLAM molecules, we demonstrate that both the acyl chains on the ManLAM mannosylphosphatidylinositol anchor and the mannooligosaccharide caps play a critical role in DC-SIGN-ManLAM interaction. Finally, we report that DC-SIGN binds poorly to the PILAM and uncapped AraLAM-containing species Mycobacterium fortuitum and Mycobacterium chelonae, respectively. Interestingly, smooth colony-forming Mycobacterium avium, in which ManLAM is capped with single mannose residues, was also poorly recognized by the lectin. Altogether, our results provide molecular insight into the mechanisms of mycobacteria-DC-SIGN interaction, and suggest that DC-SIGN may act as a pattern recognition receptor and discriminate between Mycobacterium species through selective recognition of the mannose caps on LAM molecules."}

{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":211,"end":223},"obj":"Disease"},{"id":"T2","span":{"begin":250,"end":262},"obj":"Disease"},{"id":"T3","span":{"begin":355,"end":367},"obj":"Disease"},{"id":"T4","span":{"begin":506,"end":518},"obj":"Disease"},{"id":"T5","span":{"begin":817,"end":829},"obj":"Disease"},{"id":"T6","span":{"begin":1195,"end":1207},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0018076"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0018076"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0018076"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MONDO_0018076"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/MONDO_0018076"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/MONDO_0018076"}],"text":"The cell surface receptor DC-SIGN discriminates between Mycobacterium species through selective recognition of the mannose caps on lipoarabinomannan.\nInteractions between dendritic cells (DCs) and Mycobacterium tuberculosis, the etiological agent of tuberculosis, most likely play a key role in anti-mycobacterial immunity. We have recently shown that M. tuberculosis binds to and infects DCs through ligation of the DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and that M. tuberculosis mannose-capped lipoarabinomannan (ManLAM) inhibits binding of the bacilli to the lectin, suggesting that ManLAM might be a key DC-SIGN ligand. In the present study, we investigated the molecular basis of DC-SIGN ligation by LAM. Contrary to what was found for slow growing mycobacteria, such as M. tuberculosis and the vaccine strain Mycobacterium bovis bacillus Calmette-Guérin, our data demonstrate that the fast growing saprophytic species Mycobacterium smegmatis hardly binds to DC-SIGN. Consistent with the former finding, we show that M. smegmatis-derived lipoarabinomannan, which is capped by phosphoinositide residues (PILAM), exhibits a limited ability to inhibit M. tuberculosis binding to DC-SIGN. Moreover, using enzymatically demannosylated and chemically deacylated ManLAM molecules, we demonstrate that both the acyl chains on the ManLAM mannosylphosphatidylinositol anchor and the mannooligosaccharide caps play a critical role in DC-SIGN-ManLAM interaction. Finally, we report that DC-SIGN binds poorly to the PILAM and uncapped AraLAM-containing species Mycobacterium fortuitum and Mycobacterium chelonae, respectively. Interestingly, smooth colony-forming Mycobacterium avium, in which ManLAM is capped with single mannose residues, was also poorly recognized by the lectin. Altogether, our results provide molecular insight into the mechanisms of mycobacteria-DC-SIGN interaction, and suggest that DC-SIGN may act as a pattern recognition receptor and discriminate between Mycobacterium species through selective recognition of the mannose caps on LAM molecules."}

{"project":"Lectin-Jamboree-small","denotations":[{"id":"T1","span":{"begin":26,"end":33},"obj":"Lectin"},{"id":"T2","span":{"begin":485,"end":492},"obj":"Lectin"},{"id":"T3","span":{"begin":646,"end":653},"obj":"Lectin"},{"id":"T4","span":{"begin":723,"end":730},"obj":"Lectin"},{"id":"T5","span":{"begin":1002,"end":1009},"obj":"Lectin"},{"id":"T6","span":{"begin":1219,"end":1226},"obj":"Lectin"},{"id":"T7","span":{"begin":1466,"end":1473},"obj":"Lectin"},{"id":"T8","span":{"begin":1518,"end":1525},"obj":"Lectin"},{"id":"T9","span":{"begin":1899,"end":1906},"obj":"Lectin"},{"id":"T10","span":{"begin":1937,"end":1944},"obj":"Lectin"}],"attributes":[{"id":"A1","pred":"glycosmos_id","subj":"T1","obj":"GL_001382"},{"id":"A2","pred":"glycosmos_id","subj":"T2","obj":"GL_001382"},{"id":"A3","pred":"glycosmos_id","subj":"T3","obj":"GL_001382"},{"id":"A4","pred":"glycosmos_id","subj":"T4","obj":"GL_001382"},{"id":"A5","pred":"glycosmos_id","subj":"T5","obj":"GL_001382"},{"id":"A6","pred":"glycosmos_id","subj":"T6","obj":"GL_001382"},{"id":"A7","pred":"glycosmos_id","subj":"T7","obj":"GL_001382"},{"id":"A8","pred":"glycosmos_id","subj":"T8","obj":"GL_001382"},{"id":"A9","pred":"glycosmos_id","subj":"T9","obj":"GL_001382"},{"id":"A10","pred":"glycosmos_id","subj":"T10","obj":"GL_001382"}],"namespaces":[{"prefix":"_base","uri":"https://glycosmos.org/lectins/"}],"text":"The cell surface receptor DC-SIGN discriminates between Mycobacterium species through selective recognition of the mannose caps on lipoarabinomannan.\nInteractions between dendritic cells (DCs) and Mycobacterium tuberculosis, the etiological agent of tuberculosis, most likely play a key role in anti-mycobacterial immunity. We have recently shown that M. tuberculosis binds to and infects DCs through ligation of the DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and that M. tuberculosis mannose-capped lipoarabinomannan (ManLAM) inhibits binding of the bacilli to the lectin, suggesting that ManLAM might be a key DC-SIGN ligand. In the present study, we investigated the molecular basis of DC-SIGN ligation by LAM. Contrary to what was found for slow growing mycobacteria, such as M. tuberculosis and the vaccine strain Mycobacterium bovis bacillus Calmette-Guérin, our data demonstrate that the fast growing saprophytic species Mycobacterium smegmatis hardly binds to DC-SIGN. Consistent with the former finding, we show that M. smegmatis-derived lipoarabinomannan, which is capped by phosphoinositide residues (PILAM), exhibits a limited ability to inhibit M. tuberculosis binding to DC-SIGN. Moreover, using enzymatically demannosylated and chemically deacylated ManLAM molecules, we demonstrate that both the acyl chains on the ManLAM mannosylphosphatidylinositol anchor and the mannooligosaccharide caps play a critical role in DC-SIGN-ManLAM interaction. Finally, we report that DC-SIGN binds poorly to the PILAM and uncapped AraLAM-containing species Mycobacterium fortuitum and Mycobacterium chelonae, respectively. Interestingly, smooth colony-forming Mycobacterium avium, in which ManLAM is capped with single mannose residues, was also poorly recognized by the lectin. Altogether, our results provide molecular insight into the mechanisms of mycobacteria-DC-SIGN interaction, and suggest that DC-SIGN may act as a pattern recognition receptor and discriminate between Mycobacterium species through selective recognition of the mannose caps on LAM molecules."}

{"project":"Lectin-Jamboree-Sentence","blocks":[{"id":"T1","span":{"begin":0,"end":149},"obj":"Sentence"},{"id":"T2","span":{"begin":150,"end":323},"obj":"Sentence"},{"id":"T3","span":{"begin":324,"end":661},"obj":"Sentence"},{"id":"T4","span":{"begin":662,"end":747},"obj":"Sentence"},{"id":"T5","span":{"begin":748,"end":1010},"obj":"Sentence"},{"id":"T6","span":{"begin":1011,"end":1227},"obj":"Sentence"},{"id":"T7","span":{"begin":1228,"end":1493},"obj":"Sentence"},{"id":"T8","span":{"begin":1494,"end":1656},"obj":"Sentence"},{"id":"T9","span":{"begin":1657,"end":1812},"obj":"Sentence"},{"id":"T10","span":{"begin":1813,"end":2101},"obj":"Sentence"}],"text":"The cell surface receptor DC-SIGN discriminates between Mycobacterium species through selective recognition of the mannose caps on lipoarabinomannan.\nInteractions between dendritic cells (DCs) and Mycobacterium tuberculosis, the etiological agent of tuberculosis, most likely play a key role in anti-mycobacterial immunity. We have recently shown that M. tuberculosis binds to and infects DCs through ligation of the DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and that M. tuberculosis mannose-capped lipoarabinomannan (ManLAM) inhibits binding of the bacilli to the lectin, suggesting that ManLAM might be a key DC-SIGN ligand. In the present study, we investigated the molecular basis of DC-SIGN ligation by LAM. Contrary to what was found for slow growing mycobacteria, such as M. tuberculosis and the vaccine strain Mycobacterium bovis bacillus Calmette-Guérin, our data demonstrate that the fast growing saprophytic species Mycobacterium smegmatis hardly binds to DC-SIGN. Consistent with the former finding, we show that M. smegmatis-derived lipoarabinomannan, which is capped by phosphoinositide residues (PILAM), exhibits a limited ability to inhibit M. tuberculosis binding to DC-SIGN. Moreover, using enzymatically demannosylated and chemically deacylated ManLAM molecules, we demonstrate that both the acyl chains on the ManLAM mannosylphosphatidylinositol anchor and the mannooligosaccharide caps play a critical role in DC-SIGN-ManLAM interaction. Finally, we report that DC-SIGN binds poorly to the PILAM and uncapped AraLAM-containing species Mycobacterium fortuitum and Mycobacterium chelonae, respectively. Interestingly, smooth colony-forming Mycobacterium avium, in which ManLAM is capped with single mannose residues, was also poorly recognized by the lectin. Altogether, our results provide molecular insight into the mechanisms of mycobacteria-DC-SIGN interaction, and suggest that DC-SIGN may act as a pattern recognition receptor and discriminate between Mycobacterium species through selective recognition of the mannose caps on LAM molecules."}

{"project":"NCBITAXON","denotations":[{"id":"T1","span":{"begin":56,"end":69},"obj":"OrganismTaxon"},{"id":"T2","span":{"begin":197,"end":223},"obj":"OrganismTaxon"},{"id":"T3","span":{"begin":585,"end":592},"obj":"OrganismTaxon"},{"id":"T4","span":{"begin":853,"end":866},"obj":"OrganismTaxon"},{"id":"T5","span":{"begin":873,"end":881},"obj":"OrganismTaxon"},{"id":"T7","span":{"begin":962,"end":985},"obj":"OrganismTaxon"},{"id":"T8","span":{"begin":1591,"end":1614},"obj":"OrganismTaxon"},{"id":"T9","span":{"begin":1619,"end":1632},"obj":"OrganismTaxon"},{"id":"T10","span":{"begin":1694,"end":1713},"obj":"OrganismTaxon"},{"id":"T11","span":{"begin":2012,"end":2025},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"1763"},{"id":"A2","pred":"db_id","subj":"T2","obj":"1773"},{"id":"A3","pred":"db_id","subj":"T3","obj":"91061"},{"id":"A4","pred":"db_id","subj":"T4","obj":"1763"},{"id":"A5","pred":"db_id","subj":"T5","obj":"1386"},{"id":"A6","pred":"db_id","subj":"T5","obj":"55087"},{"id":"A7","pred":"db_id","subj":"T7","obj":"1772"},{"id":"A8","pred":"db_id","subj":"T8","obj":"1766"},{"id":"A9","pred":"db_id","subj":"T9","obj":"1763"},{"id":"A10","pred":"db_id","subj":"T10","obj":"1764"},{"id":"A11","pred":"db_id","subj":"T11","obj":"1763"}],"text":"The cell surface receptor DC-SIGN discriminates between Mycobacterium species through selective recognition of the mannose caps on lipoarabinomannan.\nInteractions between dendritic cells (DCs) and Mycobacterium tuberculosis, the etiological agent of tuberculosis, most likely play a key role in anti-mycobacterial immunity. We have recently shown that M. tuberculosis binds to and infects DCs through ligation of the DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and that M. tuberculosis mannose-capped lipoarabinomannan (ManLAM) inhibits binding of the bacilli to the lectin, suggesting that ManLAM might be a key DC-SIGN ligand. In the present study, we investigated the molecular basis of DC-SIGN ligation by LAM. Contrary to what was found for slow growing mycobacteria, such as M. tuberculosis and the vaccine strain Mycobacterium bovis bacillus Calmette-Guérin, our data demonstrate that the fast growing saprophytic species Mycobacterium smegmatis hardly binds to DC-SIGN. Consistent with the former finding, we show that M. smegmatis-derived lipoarabinomannan, which is capped by phosphoinositide residues (PILAM), exhibits a limited ability to inhibit M. tuberculosis binding to DC-SIGN. Moreover, using enzymatically demannosylated and chemically deacylated ManLAM molecules, we demonstrate that both the acyl chains on the ManLAM mannosylphosphatidylinositol anchor and the mannooligosaccharide caps play a critical role in DC-SIGN-ManLAM interaction. Finally, we report that DC-SIGN binds poorly to the PILAM and uncapped AraLAM-containing species Mycobacterium fortuitum and Mycobacterium chelonae, respectively. Interestingly, smooth colony-forming Mycobacterium avium, in which ManLAM is capped with single mannose residues, was also poorly recognized by the lectin. Altogether, our results provide molecular insight into the mechanisms of mycobacteria-DC-SIGN interaction, and suggest that DC-SIGN may act as a pattern recognition receptor and discriminate between Mycobacterium species through selective recognition of the mannose caps on LAM molecules."}

{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":171,"end":186},"obj":"Body_part"},{"id":"T2","span":{"begin":188,"end":191},"obj":"Body_part"},{"id":"T3","span":{"begin":389,"end":392},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL_0000451"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL_0000451"},{"id":"A3","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/CL_0000451"}],"text":"The cell surface receptor DC-SIGN discriminates between Mycobacterium species through selective recognition of the mannose caps on lipoarabinomannan.\nInteractions between dendritic cells (DCs) and Mycobacterium tuberculosis, the etiological agent of tuberculosis, most likely play a key role in anti-mycobacterial immunity. We have recently shown that M. tuberculosis binds to and infects DCs through ligation of the DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and that M. tuberculosis mannose-capped lipoarabinomannan (ManLAM) inhibits binding of the bacilli to the lectin, suggesting that ManLAM might be a key DC-SIGN ligand. In the present study, we investigated the molecular basis of DC-SIGN ligation by LAM. Contrary to what was found for slow growing mycobacteria, such as M. tuberculosis and the vaccine strain Mycobacterium bovis bacillus Calmette-Guérin, our data demonstrate that the fast growing saprophytic species Mycobacterium smegmatis hardly binds to DC-SIGN. Consistent with the former finding, we show that M. smegmatis-derived lipoarabinomannan, which is capped by phosphoinositide residues (PILAM), exhibits a limited ability to inhibit M. tuberculosis binding to DC-SIGN. Moreover, using enzymatically demannosylated and chemically deacylated ManLAM molecules, we demonstrate that both the acyl chains on the ManLAM mannosylphosphatidylinositol anchor and the mannooligosaccharide caps play a critical role in DC-SIGN-ManLAM interaction. Finally, we report that DC-SIGN binds poorly to the PILAM and uncapped AraLAM-containing species Mycobacterium fortuitum and Mycobacterium chelonae, respectively. Interestingly, smooth colony-forming Mycobacterium avium, in which ManLAM is capped with single mannose residues, was also poorly recognized by the lectin. Altogether, our results provide molecular insight into the mechanisms of mycobacteria-DC-SIGN interaction, and suggest that DC-SIGN may act as a pattern recognition receptor and discriminate between Mycobacterium species through selective recognition of the mannose caps on LAM molecules."}

{"project":"CL-cell","denotations":[{"id":"T1","span":{"begin":171,"end":186},"obj":"Cell"},{"id":"T3","span":{"begin":188,"end":191},"obj":"Cell"},{"id":"T4","span":{"begin":389,"end":392},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0000451"},{"id":"A2","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0001056"},{"id":"A3","pred":"cl_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/CL:0000451"},{"id":"A4","pred":"cl_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/CL:0000451"}],"text":"The cell surface receptor DC-SIGN discriminates between Mycobacterium species through selective recognition of the mannose caps on lipoarabinomannan.\nInteractions between dendritic cells (DCs) and Mycobacterium tuberculosis, the etiological agent of tuberculosis, most likely play a key role in anti-mycobacterial immunity. We have recently shown that M. tuberculosis binds to and infects DCs through ligation of the DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and that M. tuberculosis mannose-capped lipoarabinomannan (ManLAM) inhibits binding of the bacilli to the lectin, suggesting that ManLAM might be a key DC-SIGN ligand. In the present study, we investigated the molecular basis of DC-SIGN ligation by LAM. Contrary to what was found for slow growing mycobacteria, such as M. tuberculosis and the vaccine strain Mycobacterium bovis bacillus Calmette-Guérin, our data demonstrate that the fast growing saprophytic species Mycobacterium smegmatis hardly binds to DC-SIGN. Consistent with the former finding, we show that M. smegmatis-derived lipoarabinomannan, which is capped by phosphoinositide residues (PILAM), exhibits a limited ability to inhibit M. tuberculosis binding to DC-SIGN. Moreover, using enzymatically demannosylated and chemically deacylated ManLAM molecules, we demonstrate that both the acyl chains on the ManLAM mannosylphosphatidylinositol anchor and the mannooligosaccharide caps play a critical role in DC-SIGN-ManLAM interaction. Finally, we report that DC-SIGN binds poorly to the PILAM and uncapped AraLAM-containing species Mycobacterium fortuitum and Mycobacterium chelonae, respectively. Interestingly, smooth colony-forming Mycobacterium avium, in which ManLAM is capped with single mannose residues, was also poorly recognized by the lectin. Altogether, our results provide molecular insight into the mechanisms of mycobacteria-DC-SIGN interaction, and suggest that DC-SIGN may act as a pattern recognition receptor and discriminate between Mycobacterium species through selective recognition of the mannose caps on LAM molecules."}