title: Differential interaction of dendritic cells with Rickettsia conorii: impact on host susceptibility to murine spotted fever rickettsiosis.
abstract: Spotted fever group rickettsioses are emerging and reemerging infectious diseases, some of which are life-threatening. In order to understand how dendritic cells (DCs) contribute to the host resistance or susceptibility to rickettsial diseases, we first characterized the in vitro interaction of rickettsiae with bone marrow-derived DCs (BMDCs) from resistant C57BL/6 (B6) and susceptible C3H/HeN (C3H) mice. In contrast to the exclusively cytosolic localization within endothelial cells, rickettsiae efficiently entered and localized in both phagosomes and cytosol of BMDCs from both mouse strains. Rickettsia conorii-infected BMDCs from resistant mice harbored higher bacterial loads compared to C3H mice. R. conorii infection induced maturation of BMDCs from both mouse strains as judged by upregulated expression of classical major histocompatibility complex (MHC) and costimulatory molecules. Compared to C3H counterparts, B6 BMDCs exhibited higher expression levels of MHC class II and higher interleukin-12 (IL-12) p40 production upon rickettsial infection and were more potent in priming naïve CD4(+) T cells to produce gamma interferon. In vitro DC infection and T-cell priming studies suggested a delayed CD4(+) T-cell activation and suppressed Th1/Th2 cell development in C3H mice. The suppressive CD4(+) T-cell responses seen in C3H mice were associated with a high frequency of Foxp3(+) T regulatory cells promoted by syngeneic R. conorii-infected BMDCs in the presence of IL-2. These data suggest that rickettsiae can target DCs to stimulate a protective type 1 response in resistant hosts but suppressive adaptive immunity in susceptible hosts.
authors.affiliation: Center for Biodefense and Emerging Infectious Diseases, 301 University Blvd., Galveston, TX 77555-0609, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Fang
authors.forename: Nahed
authors.initials: N
authors.lastname: Ismail
authors.forename: Lynn
authors.initials: L
authors.lastname: Soong
authors.forename: Vsevolod L
authors.initials: VL
authors.lastname: Popov
authors.forename: Ted
authors.initials: T
authors.lastname: Whitworth
authors.forename: Donald H
authors.initials: DH
authors.lastname: Bouyer
authors.forename: David H
authors.initials: DH
authors.lastname: Walker
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology*; D001907:Boutonneuse Fever / Q000276:immunology*; D018929:Cell Culture Techniques; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D020114:Rickettsia conorii / Q000502:physiology*; D017282:Tick-Borne Diseases / Q000276:immunology* / Q000382:microbiology