258 334

Cited 6 times in

Virulence-dependent induction of interleukin-10-producing-tolerogenic dendritic cells by Mycobacterium tuberculosis impedes optimal T helper type 1 proliferation

DC Field Value Language
dc.contributor.author신성재-
dc.date.accessioned2018-07-20T07:38:51Z-
dc.date.available2018-07-20T07:38:51Z-
dc.date.issued2017-
dc.identifier.issn0019-2805-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/160376-
dc.description.abstractMycobacterium tuberculosis inhibits optimal T helper type 1 (Th1) responses during infection. However, the precise mechanisms by which virulent M. tuberculosis limits Th1 responses remain unclear. Here, we infected dendritic cells (DCs) with the virulent M. tuberculosis strain H37Rv or the attenuated strain H37Ra to investigate the phenotypic and functional alterations in DCs and resultant T-cell responses. H37Rv-infected DCs suppressed Th1 responses more strongly than H37Ra-infected DCs. Interestingly, H37Rv, but not H37Ra, impaired DC surface molecule expression (CD80, CD86 and MHC class II) due to prominent interleukin-10 (IL-10) production while augmenting the expression of tolerogenic molecules including PD-L1, CD103, Tim-3 and indoleamine 2,3-dioxygenase on DCs in a multiplicity-of-infection (MOI) -dependent manner. These results indicate that virulent M. tuberculosis drives immature DCs toward a tolerogenic phenotype. Notably, the tolerogenic phenotype of H37Rv-infected DCs was blocked in DCs generated from IL-10-/- mice or DCs treated with an IL-10-neutralizing monoclonal antibody, leading to restoration of Th1 polarization. These findings suggest that IL-10 induces a tolerogenic DC phenotype. Interestingly, p38 mitogen-activated protein kinase (MAPK) activation predominantly mediates IL-10 production; hence, H37Rv tends to induce a tolerogenic DC phenotype through expression of tolerogenic molecules in the p38 MAPK-IL-10 axis. Therefore, suppressing the tolerogenic cascade in DCs is a novel strategy for stimulating optimal protective T-cell responses against M. tuberculosis infection.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherBlackwell Scientific Publications-
dc.relation.isPartOfIMMUNOLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnimals-
dc.subject.MESHCell Proliferation-
dc.subject.MESHDendritic Cells/immunology*-
dc.subject.MESHDendritic Cells/metabolism-
dc.subject.MESHInterleukin-10/biosynthesis*-
dc.subject.MESHInterleukin-10/deficiency-
dc.subject.MESHInterleukin-10/immunology-
dc.subject.MESHMice-
dc.subject.MESHMice, Inbred C57BL-
dc.subject.MESHMice, Transgenic-
dc.subject.MESHMycobacterium tuberculosis/immunology*-
dc.subject.MESHTh1 Cells/cytology*-
dc.subject.MESHTh1 Cells/immunology*-
dc.subject.MESHVirulence/immunology-
dc.titleVirulence-dependent induction of interleukin-10-producing-tolerogenic dendritic cells by Mycobacterium tuberculosis impedes optimal T helper type 1 proliferation-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Microbiology-
dc.contributor.googleauthorHongmin Kim-
dc.contributor.googleauthorKee Woong Kwon-
dc.contributor.googleauthorWoo Sik Kim-
dc.contributor.googleauthorSung Jae Shin-
dc.identifier.doi10.1111/imm.12721-
dc.contributor.localIdA02114-
dc.relation.journalcodeJ01036-
dc.identifier.eissn1365-2567-
dc.identifier.pmid28140445-
dc.subject.keywordTh1-type T-cell proliferation-
dc.subject.keywordinterleukin-10-
dc.subject.keywordp38 mitogen-activated protein kinase-
dc.subject.keywordtolerogenic dendritic cells-
dc.subject.keywordvirulence-
dc.contributor.alternativeNameShin, Sung Jae-
dc.contributor.affiliatedAuthorShin, Sung Jae-
dc.citation.volume151-
dc.citation.number2-
dc.citation.startPage177-
dc.citation.endPage190-
dc.identifier.bibliographicCitationIMMUNOLOGY, Vol.151(2) : 177-190, 2017-
dc.identifier.rimsid43535-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.