Orientia tsutsugamushi subverts dendritic cell functions by escaping from autophagy and impairing their migration

• Published in: PLoS neglected tropical diseases Vol. 7; no. 1; p. e1981
• Main Authors: Choi, Ji-Hye, Cheong, Taek-Chin, Ha, Na-Young, Ko, Youngho, Cho, Chung-Hyun, Jeon, Ju-Hong, So, Insuk, Kim, In-Kyu, Choi, Myung-Sik, Kim, Ik-Sang, Cho, Nam-Hyuk
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.01.2013; Public Library of Science (PLoS)
• Subjects: Animals; Antigens; Autophagy; Autophagy (Cytology); Bacteria; Bacterial infections; Biology; Bone marrow; Cell Movement; Chemokines; Cytokines; Cytokines - secretion; Demographic aspects; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - microbiology; Histocompatibility Antigens Class II - metabolism; Immune Evasion; Infections; Kinases; Lymphatic system; Lymphocytes; Medicine; Mice; Orientia tsutsugamushi; Orientia tsutsugamushi - immunology; Orientia tsutsugamushi - physiology; Pathogens; Physiological aspects; Scrub typhus; T cells; Tropical diseases; Typhus; Animals; Dendritic Cells; Immune Evasion; Cytokines; Histocompatibility Antigens Class II; Mice; Orientia tsutsugamushi; Autophagy; Cell Movement
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0001981

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. 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. 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.