Orientia tsutsugamushi subverts dendritic cell functions by escaping from autophagy and impairing their migration.
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 histoco...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | http://europepmc.org/articles/PMC3536799?pdf=render |
| _version_ | 1819113443378069504 |
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| author | Ji-Hye Choi Taek-Chin Cheong Na-Young Ha Youngho Ko Chung-Hyun Cho Ju-Hong Jeon Insuk So In-Kyu Kim Myung-Sik Choi Ik-Sang Kim Nam-Hyuk Cho |
| author_facet | Ji-Hye Choi Taek-Chin Cheong Na-Young Ha Youngho Ko Chung-Hyun Cho Ju-Hong Jeon Insuk So In-Kyu Kim Myung-Sik Choi Ik-Sang Kim Nam-Hyuk Cho |
| author_sort | Ji-Hye Choi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T04:29:29Z |
| format | Article |
| id | doaj.art-79824e88e8ee486d873483a49e4972ae |
| institution | Directory Open Access Journal |
| issn | 1935-2735 |
| language | English |
| last_indexed | 2024-12-22T04:29:29Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-79824e88e8ee486d873483a49e4972ae2022-12-21T18:39:04ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27352013-01-0171e198110.1371/journal.pntd.0001981Orientia tsutsugamushi subverts dendritic cell functions by escaping from autophagy and impairing their migration.Ji-Hye ChoiTaek-Chin CheongNa-Young HaYoungho KoChung-Hyun ChoJu-Hong JeonInsuk SoIn-Kyu KimMyung-Sik ChoiIk-Sang KimNam-Hyuk ChoBACKGROUND: 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.http://europepmc.org/articles/PMC3536799?pdf=render |
| spellingShingle | Ji-Hye Choi Taek-Chin Cheong Na-Young Ha Youngho Ko Chung-Hyun Cho Ju-Hong Jeon Insuk So In-Kyu Kim Myung-Sik Choi Ik-Sang Kim Nam-Hyuk Cho Orientia tsutsugamushi subverts dendritic cell functions by escaping from autophagy and impairing their migration. PLoS Neglected Tropical Diseases |
| title | Orientia tsutsugamushi subverts dendritic cell functions by escaping from autophagy and impairing their migration. |
| title_full | Orientia tsutsugamushi subverts dendritic cell functions by escaping from autophagy and impairing their migration. |
| title_fullStr | Orientia tsutsugamushi subverts dendritic cell functions by escaping from autophagy and impairing their migration. |
| title_full_unstemmed | Orientia tsutsugamushi subverts dendritic cell functions by escaping from autophagy and impairing their migration. |
| title_short | Orientia tsutsugamushi subverts dendritic cell functions by escaping from autophagy and impairing their migration. |
| title_sort | orientia tsutsugamushi subverts dendritic cell functions by escaping from autophagy and impairing their migration |
| url | http://europepmc.org/articles/PMC3536799?pdf=render |
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