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사진없음
최지혜 (Ji-Hye Choi)
서울대학교 의과대학
조회 1775  인쇄하기 주소복사 트위터 공유 페이스북 공유 
Orientia tsutsugamushi Subverts Dendritic Cell Functions by Escaping from Autophagy and Impairing Their Migration

Ji-Hye Choi1, Taek-Chin Cheong1, Na-Young Ha1, Youngho Ko1, Chung-Hyun Cho2, Ju-Hong Jeon3, Insuk So3, In-Kyu Kim4, Myung-Sik Choi1, Ik-Sang Kim1, Nam-Hyuk Cho1,5*

1 Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea, 2 Pharmacology, Seoul National University College of Medicine, Seoul, Republic of Korea, 3 Physiology, Seoul National University College of Medicine, Seoul, Republic of Korea, 4 Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Republic of Korea, 5 Institute of Endemic Disease, Seoul National University Medical Research Center and Bundang Hospital, Jongno-Gu, Seoul, Republic of Korea

Abstract

Background
Dendritic cells (DCs) are the most potent antigen-presenting cells that link innate and adaptive immune responses, playing a pivotal role in triggering antigen-specific immunity. Antigen uptake by DCs induces maturational changes that include increased surface expression of major histocompatibility complex (MHC) and costimulatory molecules. In addition, DCs actively migrate to regional lymph nodes and activate antigen-specific naive T cells after capturing antigens. We characterize the functional changes of DCs infected with Orientia tsutsugamushi, the causative agent of scrub typhus, since there is limited knowledge of the role played by DCs in O. tsutsugamushi infection.

Methodology/Principal Finding
O. tsutsugamushi efficiently infected bone marrow-derived DCs and induced surface expression of MHC II and costimulatory molecules. In addition, O. tsutsugamushi induced autophagy activation, but actively escaped from this innate defense system. Infected DCs also secreted cytokines and chemokines such as IL-6, IL-12, MCP5, MIP-1α, and RANTES. Furthermore, in vitro migration of DCs in the presence of a CCL19 gradient within a 3D collagen matrix was drastically impaired when infected with O. tsutsugamushi. The infected cells migrated much less efficiently into lymphatic vessels of ear dermis ex vivo when compared to LPS-stimulated DCs. In vivo migration of O. tsutsugamushi-infected DCs to regional lymph nodes was significantly impaired and similar to that of immature DCs. Finally, we found that MAP kinases involved in chemotactic signaling were differentially activated in O. tsutsugamushi-infected DCs.

Conclusion/Significance
These results suggest that O. tsutsugamushi can target DCs to exploit these sentinel cells as replication reservoirs and delay or impair the functional maturation of DCs during the bacterial infection in mammals.

논문정보 F1000선정
- 형식: Research article
- 게재일: 2013년 01월 (BRIC 등록일 2014-05-30)
- 연구진: 국내연구진태극기
- 분야: Parasitology
- 추천: Faculty of 1000 Biology
- 추천사유: F1000Prime Recommendations, Dissents and Comments for [Choi JH et al., PLoS Negl Trop Dis 2013, 7(1):e1981]. In F1000Prime, 26 May 2014; F1000Prime.com/718402458
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박옥현
발표: 박옥현 (고려대학교)
일자: 2019년 6월 21일 (금) 오후 02시 (한국시간)
언어: 한국어
참석자 접수신청하기
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정현환
발표: 정현환 (Baylor College of Medicine, Texas C...)
일자: 2019년 6월 26일 (수) 오전 10시 (한국시간)
언어:
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Parasitology

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