Rickettsiae-Stimulated Dendritic Cells Mediate Protection against Lethal Rickettsial Challenge in an Animal Model of Spotted Fever Rickettsiosis

The role played by dendritic cells (DCs), initiators and orchestrators of the immune response, remains unclear in rickettsial infections. To investigate their importance in rickettsioses, we analyzed the responses of murine bone marrow-derived DCs (BMDCs) after rickettsial stimulation in vitro and t...

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Published in:The Journal of infectious diseases 2007-08, Vol.196 (4), p.629-638
Main Authors: Jordan, Jeffrey M., Woods, Michael E., Feng, Hui-Min, Soong, Lynn, Walker, David H.
Format: Article
Language:English
Subjects:
Animals
Antigens
B7-1 Antigen - metabolism
B7-2 Antigen - metabolism
Bacteria
Bacterial diseases
Biological and medical sciences
Bone Marrow - immunology
Boutonneuse Fever - immunology
Boutonneuse Fever - prevention & control
CD40 Antigens - metabolism
Cells, Cultured
Coculture Techniques
Cytokines
Dendritic cells
Dendritic Cells - immunology
Dendritic Cells - metabolism
Dendritic Cells - transplantation
Histocompatibility Antigens Class II - metabolism
Human bacterial diseases
Immunity
Infections
Infectious diseases
Interferon-gamma - biosynthesis
Interferon-gamma - immunology
Interleukins - biosynthesis
Male
Medical sciences
Mice
Mice, Inbred C3H
Natural killer cells
Rickettsia
Rickettsia conorii
Rickettsial diseases
Species Specificity
Spleen
T lymphocytes
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Tropical bacterial diseases
Up-Regulation
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container_issue 4
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container_title The Journal of infectious diseases
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creator Jordan, Jeffrey M.
Woods, Michael E.
Feng, Hui-Min
Soong, Lynn
Walker, David H.
description The role played by dendritic cells (DCs), initiators and orchestrators of the immune response, remains unclear in rickettsial infections. To investigate their importance in rickettsioses, we analyzed the responses of murine bone marrow-derived DCs (BMDCs) after rickettsial stimulation in vitro and their protective role in vivo. Rickettsia conorii stimulation of BMDCs caused significant maturation and production of proinflammatory cytokines. Transfer of rickettsiae-stimulated DCs protected mice from lethal rickettsial challenge by limiting rickettsial proliferation in vivo, whereas partial protection was observed in mice receiving lipopolysaccharide (LPS)-stimulated DCs. Immunity to R. conorii after transfer of DCs was associated with up-regulation of CD40, CD80, CD86, and major histocompatibility complex class II; with production of IL-2, IL-12, and IL23; and with production of antigen-specific interferon-γ in T cells. Taken together, our data suggest that a vigorous proinflammatory response in DCs is associated with protective immunity to rickettsiae and that generation of antigen-specific immunity is crucial to complete protection.
doi_str_mv 10.1086/519686
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To investigate their importance in rickettsioses, we analyzed the responses of murine bone marrow-derived DCs (BMDCs) after rickettsial stimulation in vitro and their protective role in vivo. Rickettsia conorii stimulation of BMDCs caused significant maturation and production of proinflammatory cytokines. Transfer of rickettsiae-stimulated DCs protected mice from lethal rickettsial challenge by limiting rickettsial proliferation in vivo, whereas partial protection was observed in mice receiving lipopolysaccharide (LPS)-stimulated DCs. Immunity to R. conorii after transfer of DCs was associated with up-regulation of CD40, CD80, CD86, and major histocompatibility complex class II; with production of IL-2, IL-12, and IL23; and with production of antigen-specific interferon-γ in T cells. 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subjects Animals
Antigens
B7-1 Antigen - metabolism
B7-2 Antigen - metabolism
Bacteria
Bacterial diseases
Biological and medical sciences
Bone Marrow - immunology
Boutonneuse Fever - immunology
Boutonneuse Fever - prevention & control
CD40 Antigens - metabolism
Cells, Cultured
Coculture Techniques
Cytokines
Dendritic cells
Dendritic Cells - immunology
Dendritic Cells - metabolism
Dendritic Cells - transplantation
Histocompatibility Antigens Class II - metabolism
Human bacterial diseases
Immunity
Infections
Infectious diseases
Interferon-gamma - biosynthesis
Interferon-gamma - immunology
Interleukins - biosynthesis
Male
Medical sciences
Mice
Mice, Inbred C3H
Natural killer cells
Rickettsia
Rickettsia conorii
Rickettsial diseases
Species Specificity
Spleen
T lymphocytes
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Tropical bacterial diseases
Up-Regulation
title Rickettsiae-Stimulated Dendritic Cells Mediate Protection against Lethal Rickettsial Challenge in an Animal Model of Spotted Fever Rickettsiosis
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