PMID- 23301113
OWN - NLM
STAT- MEDLINE
DCOM- 20130619
LR  - 20211021
IS  - 1935-2735 (Electronic)
IS  - 1935-2727 (Print)
IS  - 1935-2727 (Linking)
VI  - 7
IP  - 1
DP  - 2013
TI  - Orientia tsutsugamushi subverts dendritic cell functions by escaping from 
      autophagy and impairing their migration.
PG  - e1981
LID - 10.1371/journal.pntd.0001981 [doi]
LID - e1981
AB  - 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-1alpha, 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.
FAU - Choi, Ji-Hye
AU  - Choi JH
AD  - Department of Microbiology and Immunology, Seoul National University College of 
      Medicine, Seoul, Republic of Korea.
FAU - Cheong, Taek-Chin
AU  - Cheong TC
FAU - Ha, Na-Young
AU  - Ha NY
FAU - Ko, Youngho
AU  - Ko Y
FAU - Cho, Chung-Hyun
AU  - Cho CH
FAU - Jeon, Ju-Hong
AU  - Jeon JH
FAU - So, Insuk
AU  - So I
FAU - Kim, In-Kyu
AU  - Kim IK
FAU - Choi, Myung-Sik
AU  - Choi MS
FAU - Kim, Ik-Sang
AU  - Kim IS
FAU - Cho, Nam-Hyuk
AU  - Cho NH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130103
PL  - United States
TA  - PLoS Negl Trop Dis
JT  - PLoS neglected tropical diseases
JID - 101291488
RN  - 0 (Cytokines)
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
MH  - Animals
MH  - *Autophagy
MH  - *Cell Movement
MH  - Cytokines/metabolism
MH  - Dendritic Cells/*immunology/*microbiology
MH  - Histocompatibility Antigens Class II/metabolism
MH  - *Immune Evasion
MH  - Mice
MH  - Orientia tsutsugamushi/*immunology/physiology
PMC - PMC3536799
COIS- The authors have declared that no competing interests exist.
EDAT- 2013/01/10 06:00
MHDA- 2013/06/20 06:00
PMCR- 2013/01/03
CRDT- 2013/01/10 06:00
PHST- 2012/07/01 00:00 [received]
PHST- 2012/11/05 00:00 [accepted]
PHST- 2013/01/10 06:00 [entrez]
PHST- 2013/01/10 06:00 [pubmed]
PHST- 2013/06/20 06:00 [medline]
PHST- 2013/01/03 00:00 [pmc-release]
AID - PNTD-D-12-00811 [pii]
AID - 10.1371/journal.pntd.0001981 [doi]
PST - ppublish
SO  - PLoS Negl Trop Dis. 2013;7(1):e1981. doi: 10.1371/journal.pntd.0001981. Epub 2013 
      Jan 3.