Dendritic cells pulsed with live and dead Legionella pneumophila elicit distinct immune responses.
Legionella pneumophila is the causative pathogen of Legionnaires' disease, which is characterized by severe pneumonia. In regard to the pathophysiology of Legionella infection, the role of inflammatory phagocytes such as macrophages has been well documented, but the involvement of dendritic cells (DCs) has not been clarified. In this study, we have investigated the immune responses that DCs generate in vitro and in vivo after contact with L. pneumophila. Heat- and formalin-killed L. pneumophila, but not live L. pneumophila, induced immature DCs to undergo similar phenotypic maturation, but the secreted proinflammatory cytokines showed different patterns. The mechanisms of the DC maturation by heat- or formalin-killed L. pneumophila depended, at least in part, on Toll-like receptor 4 signaling or on Legionella LPS, respectively. After transfer to naive mice, DCs pulsed with dead Legionella produced serum Ig isotype responses specific for Legionella, leading to protective immunity against an otherwise lethal respiratory challenge with L. pneumophila. The in vivo immune responses required the Ag presentation of DCs, especially that on MHC class II molecules, and the immunity yielded cross-protection between clinical and environmental strains of L. pneumophila. Although the DC maturation was impaired by live Legionella, macrophages were activated by live as well as dead L. pneumophila, as evidenced by the up-regulation of MHC class II. Finally, DCs, but not macrophages, exhibited a proliferative response to live L. pneumophila that was consistent with their cell cycle progression. These findings provide a better understanding of the role of DCs in adaptive immunity to Legionella infection.
Kikuchi
Toshiaki
T
Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan. kikuchi@idac.tohoku.ac.jp
Kobayashi
Takao
T
Gomi
Kazunori
K
Suzuki
Takuji
T
Tokue
Yutaka
Y
Watanabe
Akira
A
Nukiwa
Toshihiro
T
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D002455:Cell Division / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology* / Q000637:transplantation; D004927:Escherichia coli Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D005260:Female; D005557:Formaldehyde; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics; D006358:Hot Temperature; D016130:Immunophenotyping; D016952:Legionella pneumophila / Q000254:growth & development* / Q000276:immunology*; D007877:Legionnaires' Disease / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011956:Receptors, Cell Surface / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D051193:Toll-Like Receptors
D000907:Antibodies, Bacterial; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D005557:Formaldehyde