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Neutrophils Promote Mycobacterial Trehalose Dimycolate-Induced Lung Inflammation via the Mincle Pathway

DC FieldValueLanguage
dc.contributor.author조상래-
dc.date.accessioned2014-12-19T17:37:05Z-
dc.date.available2014-12-19T17:37:05Z-
dc.date.issued2012-
dc.identifier.issn1553-7366-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/91747-
dc.description.abstractTrehalose 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.statementOfResponsibilityopen-
dc.relation.isPartOfPLOS PATHOGENS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAdjuvants, Immunologic/adverse effects*-
dc.subject.MESHAdjuvants, Immunologic/chemistry-
dc.subject.MESHAdjuvants, Immunologic/pharmacology-
dc.subject.MESHAnimals-
dc.subject.MESHCD11b Antigen/genetics-
dc.subject.MESHCD11b Antigen/immunology-
dc.subject.MESHCD11b Antigen/metabolism-
dc.subject.MESHCD18 Antigens/genetics-
dc.subject.MESHCD18 Antigens/immunology-
dc.subject.MESHCD18 Antigens/metabolism-
dc.subject.MESHCord Factors/adverse effects*-
dc.subject.MESHCord Factors/chemistry-
dc.subject.MESHCord Factors/pharmacology-
dc.subject.MESHGene Expression Regulation/drug effects-
dc.subject.MESHGene Expression Regulation/genetics-
dc.subject.MESHGene Expression Regulation/immunology-
dc.subject.MESHGranuloma, Respiratory Tract/chemically induced-
dc.subject.MESHGranuloma, Respiratory Tract/genetics-
dc.subject.MESHGranuloma, Respiratory Tract/immunology-
dc.subject.MESHGranuloma, Respiratory Tract/metabolism-
dc.subject.MESHGranuloma, Respiratory Tract/pathology-
dc.subject.MESHLectins, C-Type/genetics-
dc.subject.MESHLectins, C-Type/immunology-
dc.subject.MESHLectins, C-Type/metabolism*-
dc.subject.MESHLung/immunology-
dc.subject.MESHLung/metabolism-
dc.subject.MESHLung/pathology-
dc.subject.MESHMembrane Proteins/genetics-
dc.subject.MESHMembrane Proteins/immunology-
dc.subject.MESHMembrane Proteins/metabolism*-
dc.subject.MESHMice-
dc.subject.MESHMice, Knockout-
dc.subject.MESHMycobacterium tuberculosis/chemistry-
dc.subject.MESHMycobacterium tuberculosis/metabolism-
dc.subject.MESHNeutrophil Infiltration/drug effects*-
dc.subject.MESHNeutrophil Infiltration/genetics-
dc.subject.MESHNeutrophil Infiltration/immunology-
dc.subject.MESHNeutrophils/immunology-
dc.subject.MESHNeutrophils/metabolism*-
dc.subject.MESHNeutrophils/pathology-
dc.subject.MESHPneumonia/chemically induced*-
dc.subject.MESHPneumonia/genetics-
dc.subject.MESHPneumonia/immunology-
dc.subject.MESHPneumonia/metabolism*-
dc.subject.MESHPneumonia/pathology-
dc.subject.MESHProtein Kinases/genetics-
dc.subject.MESHProtein Kinases/immunology-
dc.subject.MESHProtein Kinases/metabolism-
dc.subject.MESHSignal Transduction/drug effects*-
dc.subject.MESHSignal Transduction/genetics-
dc.subject.MESHSignal Transduction/immunology-
dc.subject.MESHToll-Like Receptor 2/genetics-
dc.subject.MESHToll-Like Receptor 2/immunology-
dc.subject.MESHToll-Like Receptor 2/metabolism-
dc.subject.MESHTuberculosis, Pulmonary/genetics-
dc.subject.MESHTuberculosis, Pulmonary/immunology-
dc.subject.MESHTuberculosis, Pulmonary/metabolism-
dc.subject.MESHTuberculosis, Pulmonary/pathology-
dc.titleNeutrophils Promote Mycobacterial Trehalose Dimycolate-Induced Lung Inflammation via the Mincle Pathway-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Microbiology (미생물학)-
dc.contributor.googleauthorWook-Bin Lee-
dc.contributor.googleauthorJi-Seon Kang-
dc.contributor.googleauthorJi-Jing Yan-
dc.contributor.googleauthorMyeong Sup Lee-
dc.contributor.googleauthorBo-Young Jeon-
dc.contributor.googleauthorSang-Nae Cho-
dc.contributor.googleauthorYoung-Joon Kim-
dc.identifier.doi22496642-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA03824-
dc.relation.journalcodeJ02541-
dc.identifier.eissn1553-7374-
dc.identifier.pmid22496642-
dc.subject.keywordAdjuvants, Immunologic/adverse effects*-
dc.subject.keywordAdjuvants, Immunologic/chemistry-
dc.subject.keywordAdjuvants, Immunologic/pharmacology-
dc.subject.keywordAnimals-
dc.subject.keywordCD11b Antigen/genetics-
dc.subject.keywordCD11b Antigen/immunology-
dc.subject.keywordCD11b Antigen/metabolism-
dc.subject.keywordCD18 Antigens/genetics-
dc.subject.keywordCD18 Antigens/immunology-
dc.subject.keywordCD18 Antigens/metabolism-
dc.subject.keywordCord Factors/adverse effects*-
dc.subject.keywordCord Factors/chemistry-
dc.subject.keywordCord Factors/pharmacology-
dc.subject.keywordGene Expression Regulation/drug effects-
dc.subject.keywordGene Expression Regulation/genetics-
dc.subject.keywordGene Expression Regulation/immunology-
dc.subject.keywordGranuloma, Respiratory Tract/chemically induced-
dc.subject.keywordGranuloma, Respiratory Tract/genetics-
dc.subject.keywordGranuloma, Respiratory Tract/immunology-
dc.subject.keywordGranuloma, Respiratory Tract/metabolism-
dc.subject.keywordGranuloma, Respiratory Tract/pathology-
dc.subject.keywordLectins, C-Type/genetics-
dc.subject.keywordLectins, C-Type/immunology-
dc.subject.keywordLectins, C-Type/metabolism*-
dc.subject.keywordLung/immunology-
dc.subject.keywordLung/metabolism-
dc.subject.keywordLung/pathology-
dc.subject.keywordMembrane Proteins/genetics-
dc.subject.keywordMembrane Proteins/immunology-
dc.subject.keywordMembrane Proteins/metabolism*-
dc.subject.keywordMice-
dc.subject.keywordMice, Knockout-
dc.subject.keywordMycobacterium tuberculosis/chemistry-
dc.subject.keywordMycobacterium tuberculosis/metabolism-
dc.subject.keywordNeutrophil Infiltration/drug effects*-
dc.subject.keywordNeutrophil Infiltration/genetics-
dc.subject.keywordNeutrophil Infiltration/immunology-
dc.subject.keywordNeutrophils/immunology-
dc.subject.keywordNeutrophils/metabolism*-
dc.subject.keywordNeutrophils/pathology-
dc.subject.keywordPneumonia/chemically induced*-
dc.subject.keywordPneumonia/genetics-
dc.subject.keywordPneumonia/immunology-
dc.subject.keywordPneumonia/metabolism*-
dc.subject.keywordPneumonia/pathology-
dc.subject.keywordProtein Kinases/genetics-
dc.subject.keywordProtein Kinases/immunology-
dc.subject.keywordProtein Kinases/metabolism-
dc.subject.keywordSignal Transduction/drug effects*-
dc.subject.keywordSignal Transduction/genetics-
dc.subject.keywordSignal Transduction/immunology-
dc.subject.keywordToll-Like Receptor 2/genetics-
dc.subject.keywordToll-Like Receptor 2/immunology-
dc.subject.keywordToll-Like Receptor 2/metabolism-
dc.subject.keywordTuberculosis, Pulmonary/genetics-
dc.subject.keywordTuberculosis, Pulmonary/immunology-
dc.subject.keywordTuberculosis, Pulmonary/metabolism-
dc.subject.keywordTuberculosis, Pulmonary/pathology-
dc.contributor.alternativeNameCho, Sang Nae-
dc.contributor.affiliatedAuthorCho, Sang Nae-
dc.citation.volume8-
dc.citation.number4-
dc.citation.startPagee1002614-
dc.identifier.bibliographicCitationPLOS PATHOGENS, Vol.8(4) : e1002614, 2012-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers

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