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Neutrophils Promote Mycobacterial Trehalose Dimycolate-Induced Lung Inflammation via the Mincle Pathway
DC Field | Value | Language |
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dc.contributor.author | 조상래 | - |
dc.date.accessioned | 2014-12-19T17:37:05Z | - |
dc.date.available | 2014-12-19T17:37:05Z | - |
dc.date.issued | 2012 | - |
dc.identifier.issn | 1553-7366 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/91747 | - |
dc.description.abstract | Trehalose 6,6'-dimycolate (TDM), a cord factor of Mycobacterium tuberculosis (Mtb), is an important regulator of immune responses during Mtb infections. Macrophages recognize TDM through the Mincle receptor and initiate TDM-induced inflammatory responses, leading to lung granuloma formation. Although various immune cells are recruited to lung granulomas, the roles of other immune cells, especially during the initial process of TDM-induced inflammation, are not clear. In this study, Mincle signaling on neutrophils played an important role in TDM-induced lung inflammation by promoting adhesion and innate immune responses. Neutrophils were recruited during the early stage of lung inflammation following TDM-induced granuloma formation. Mincle expression on neutrophils was required for infiltration of TDM-challenged sites in a granuloma model induced by TDM-coated-beads. TDM-induced Mincle signaling on neutrophils increased cell adherence by enhancing F-actin polymerization and CD11b/CD18 surface expression. The TDM-induced effects were dependent on Src, Syk, and MAPK/ERK kinases (MEK). Moreover, coactivation of the Mincle and TLR2 pathways by TDM and Pam3CSK4 treatment synergistically induced CD11b/CD18 surface expression, reactive oxygen species, and TNFα production by neutrophils. These synergistically-enhanced immune responses correlated with the degree of Mincle expression on neutrophil surfaces. The physiological relevance of the Mincle-mediated anti-TDM immune response was confirmed by defective immune responses in Mincle⁻/⁻ mice upon aerosol infections with Mtb. Mincle-mutant mice had higher inflammation levels and mycobacterial loads than WT mice. Neutrophil depletion with anti-Ly6G antibody caused a reduction in IL-6 and monocyte chemotactic protein-1 expression upon TDM treatment, and reduced levels of immune cell recruitment during the initial stage of infection. These findings suggest a new role of Mincle signaling on neutrophils during anti-mycobacterial responses. | - |
dc.description.statementOfResponsibility | open | - |
dc.relation.isPartOf | PLOS PATHOGENS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Adjuvants, Immunologic/adverse effects* | - |
dc.subject.MESH | Adjuvants, Immunologic/chemistry | - |
dc.subject.MESH | Adjuvants, Immunologic/pharmacology | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | CD11b Antigen/genetics | - |
dc.subject.MESH | CD11b Antigen/immunology | - |
dc.subject.MESH | CD11b Antigen/metabolism | - |
dc.subject.MESH | CD18 Antigens/genetics | - |
dc.subject.MESH | CD18 Antigens/immunology | - |
dc.subject.MESH | CD18 Antigens/metabolism | - |
dc.subject.MESH | Cord Factors/adverse effects* | - |
dc.subject.MESH | Cord Factors/chemistry | - |
dc.subject.MESH | Cord Factors/pharmacology | - |
dc.subject.MESH | Gene Expression Regulation/drug effects | - |
dc.subject.MESH | Gene Expression Regulation/genetics | - |
dc.subject.MESH | Gene Expression Regulation/immunology | - |
dc.subject.MESH | Granuloma, Respiratory Tract/chemically induced | - |
dc.subject.MESH | Granuloma, Respiratory Tract/genetics | - |
dc.subject.MESH | Granuloma, Respiratory Tract/immunology | - |
dc.subject.MESH | Granuloma, Respiratory Tract/metabolism | - |
dc.subject.MESH | Granuloma, Respiratory Tract/pathology | - |
dc.subject.MESH | Lectins, C-Type/genetics | - |
dc.subject.MESH | Lectins, C-Type/immunology | - |
dc.subject.MESH | Lectins, C-Type/metabolism* | - |
dc.subject.MESH | Lung/immunology | - |
dc.subject.MESH | Lung/metabolism | - |
dc.subject.MESH | Lung/pathology | - |
dc.subject.MESH | Membrane Proteins/genetics | - |
dc.subject.MESH | Membrane Proteins/immunology | - |
dc.subject.MESH | Membrane Proteins/metabolism* | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Knockout | - |
dc.subject.MESH | Mycobacterium tuberculosis/chemistry | - |
dc.subject.MESH | Mycobacterium tuberculosis/metabolism | - |
dc.subject.MESH | Neutrophil Infiltration/drug effects* | - |
dc.subject.MESH | Neutrophil Infiltration/genetics | - |
dc.subject.MESH | Neutrophil Infiltration/immunology | - |
dc.subject.MESH | Neutrophils/immunology | - |
dc.subject.MESH | Neutrophils/metabolism* | - |
dc.subject.MESH | Neutrophils/pathology | - |
dc.subject.MESH | Pneumonia/chemically induced* | - |
dc.subject.MESH | Pneumonia/genetics | - |
dc.subject.MESH | Pneumonia/immunology | - |
dc.subject.MESH | Pneumonia/metabolism* | - |
dc.subject.MESH | Pneumonia/pathology | - |
dc.subject.MESH | Protein Kinases/genetics | - |
dc.subject.MESH | Protein Kinases/immunology | - |
dc.subject.MESH | Protein Kinases/metabolism | - |
dc.subject.MESH | Signal Transduction/drug effects* | - |
dc.subject.MESH | Signal Transduction/genetics | - |
dc.subject.MESH | Signal Transduction/immunology | - |
dc.subject.MESH | Toll-Like Receptor 2/genetics | - |
dc.subject.MESH | Toll-Like Receptor 2/immunology | - |
dc.subject.MESH | Toll-Like Receptor 2/metabolism | - |
dc.subject.MESH | Tuberculosis, Pulmonary/genetics | - |
dc.subject.MESH | Tuberculosis, Pulmonary/immunology | - |
dc.subject.MESH | Tuberculosis, Pulmonary/metabolism | - |
dc.subject.MESH | Tuberculosis, Pulmonary/pathology | - |
dc.title | Neutrophils Promote Mycobacterial Trehalose Dimycolate-Induced Lung Inflammation via the Mincle Pathway | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Microbiology (미생물학) | - |
dc.contributor.googleauthor | Wook-Bin Lee | - |
dc.contributor.googleauthor | Ji-Seon Kang | - |
dc.contributor.googleauthor | Ji-Jing Yan | - |
dc.contributor.googleauthor | Myeong Sup Lee | - |
dc.contributor.googleauthor | Bo-Young Jeon | - |
dc.contributor.googleauthor | Sang-Nae Cho | - |
dc.contributor.googleauthor | Young-Joon Kim | - |
dc.identifier.doi | 22496642 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A03824 | - |
dc.relation.journalcode | J02541 | - |
dc.identifier.eissn | 1553-7374 | - |
dc.identifier.pmid | 22496642 | - |
dc.subject.keyword | Adjuvants, Immunologic/adverse effects* | - |
dc.subject.keyword | Adjuvants, Immunologic/chemistry | - |
dc.subject.keyword | Adjuvants, Immunologic/pharmacology | - |
dc.subject.keyword | Animals | - |
dc.subject.keyword | CD11b Antigen/genetics | - |
dc.subject.keyword | CD11b Antigen/immunology | - |
dc.subject.keyword | CD11b Antigen/metabolism | - |
dc.subject.keyword | CD18 Antigens/genetics | - |
dc.subject.keyword | CD18 Antigens/immunology | - |
dc.subject.keyword | CD18 Antigens/metabolism | - |
dc.subject.keyword | Cord Factors/adverse effects* | - |
dc.subject.keyword | Cord Factors/chemistry | - |
dc.subject.keyword | Cord Factors/pharmacology | - |
dc.subject.keyword | Gene Expression Regulation/drug effects | - |
dc.subject.keyword | Gene Expression Regulation/genetics | - |
dc.subject.keyword | Gene Expression Regulation/immunology | - |
dc.subject.keyword | Granuloma, Respiratory Tract/chemically induced | - |
dc.subject.keyword | Granuloma, Respiratory Tract/genetics | - |
dc.subject.keyword | Granuloma, Respiratory Tract/immunology | - |
dc.subject.keyword | Granuloma, Respiratory Tract/metabolism | - |
dc.subject.keyword | Granuloma, Respiratory Tract/pathology | - |
dc.subject.keyword | Lectins, C-Type/genetics | - |
dc.subject.keyword | Lectins, C-Type/immunology | - |
dc.subject.keyword | Lectins, C-Type/metabolism* | - |
dc.subject.keyword | Lung/immunology | - |
dc.subject.keyword | Lung/metabolism | - |
dc.subject.keyword | Lung/pathology | - |
dc.subject.keyword | Membrane Proteins/genetics | - |
dc.subject.keyword | Membrane Proteins/immunology | - |
dc.subject.keyword | Membrane Proteins/metabolism* | - |
dc.subject.keyword | Mice | - |
dc.subject.keyword | Mice, Knockout | - |
dc.subject.keyword | Mycobacterium tuberculosis/chemistry | - |
dc.subject.keyword | Mycobacterium tuberculosis/metabolism | - |
dc.subject.keyword | Neutrophil Infiltration/drug effects* | - |
dc.subject.keyword | Neutrophil Infiltration/genetics | - |
dc.subject.keyword | Neutrophil Infiltration/immunology | - |
dc.subject.keyword | Neutrophils/immunology | - |
dc.subject.keyword | Neutrophils/metabolism* | - |
dc.subject.keyword | Neutrophils/pathology | - |
dc.subject.keyword | Pneumonia/chemically induced* | - |
dc.subject.keyword | Pneumonia/genetics | - |
dc.subject.keyword | Pneumonia/immunology | - |
dc.subject.keyword | Pneumonia/metabolism* | - |
dc.subject.keyword | Pneumonia/pathology | - |
dc.subject.keyword | Protein Kinases/genetics | - |
dc.subject.keyword | Protein Kinases/immunology | - |
dc.subject.keyword | Protein Kinases/metabolism | - |
dc.subject.keyword | Signal Transduction/drug effects* | - |
dc.subject.keyword | Signal Transduction/genetics | - |
dc.subject.keyword | Signal Transduction/immunology | - |
dc.subject.keyword | Toll-Like Receptor 2/genetics | - |
dc.subject.keyword | Toll-Like Receptor 2/immunology | - |
dc.subject.keyword | Toll-Like Receptor 2/metabolism | - |
dc.subject.keyword | Tuberculosis, Pulmonary/genetics | - |
dc.subject.keyword | Tuberculosis, Pulmonary/immunology | - |
dc.subject.keyword | Tuberculosis, Pulmonary/metabolism | - |
dc.subject.keyword | Tuberculosis, Pulmonary/pathology | - |
dc.contributor.alternativeName | Cho, Sang Nae | - |
dc.contributor.affiliatedAuthor | Cho, Sang Nae | - |
dc.citation.volume | 8 | - |
dc.citation.number | 4 | - |
dc.citation.startPage | e1002614 | - |
dc.identifier.bibliographicCitation | PLOS PATHOGENS, Vol.8(4) : e1002614, 2012 | - |
dc.identifier.rimsid | 31165 | - |
dc.type.rims | ART | - |
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