Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 370K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Shah, J. A. Articles by Seder, R. A. Search for Related Content PubMed PubMed Citation Articles by Shah, J. A. Articles by Seder, R. A. Social Bookmarking                      What's this?

Dendritic Cells Are Responsible for the Capacity of CpG Oligodeoxynucleotides to Act as an Adjuvant for Protective Vaccine Immunity Against Leishmania major in Mice

Javeed A. Shah¹, Patricia A. Darrah¹, David R. Ambrozak², Tara N. Turon¹, Susana Mendez³, Joanna Kirman¹, Chang-You Wu¹, Nicolas Glaichenhaus⁴ and Robert A. Seder¹

¹ Cellular Immunology Section, Vaccine Research Center
² Human Immunology Section, Vaccine Research Center
³ Intracellular Parasite Biology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
⁴ Centre National de la Recherche Scientifique, UMR 6097, Institute de Pharmacologie Moléculaire et Cellulaire, 06560 Valbonne, France

Address correspondence to Dr. Robert A. Seder, VRC, NIAID, 40 Convent Dr., Room 40/3512, NIH, Bethesda, MD 20892. Phone: 301-594-8483; Fax: 301-480-2565; E-mail: rseder{at}niaid.nih.gov

Vaccination with leishmanial Ag and CpG oligodeoxynucleotides (ODN) confers sustained cellular immunity and protection to infectious challenge up to 6 mo after immunization. To define the cellular mechanism by which CpG ODN mediate their adjuvant effects in vivo, the functional capacity of distinct dendritic cell (DC) subsets was assessed in the lymph nodes (LNs) of BALB/c mice, 36 h after immunization with the leishmanial antigen (LACK) and CpG ODN. After this immunization, there was a striking decrease in the frequency of the CD11c⁺B220⁺ plasmacytoid DCs with a proportionate increase in CD11c⁺CD8^-B220^- cells. CD11c⁺CD8⁺B220^- cells were the most potent producers of interleukin (IL)-12 p70 and interferon (IFN)-, while plasmacytoid DCs were the only subset capable of secreting IFN-. In terms of antigen presenting capacity, plasmacytoid DCs were far less efficient compared with the other DC subsets. To certify that DCs were responsible for effective vaccination, we isolated CD11c⁺ and CD11c^- cells 36 h after immunization and used such cells to elicit protective immunity after adoptive transfer in naive, Leishmania major susceptible BALB/c mice. CD11c⁺ cells but not 10-fold higher numbers of CD11c^- cells from such immunized mice mediated protection. Therefore, the combination of LACK antigen and CpG ODN adjuvant leads to the presence of CD11c⁺ DCs in the draining LN that are capable of vaccinating naive mice in the absence of further antigen or adjuvant.

Key Words: plasmacytoid dendritic cell • Toll-like receptor • Leishmania major • vaccine • Th1 cells

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Kool, M., Soullie, T., van Nimwegen, M., Willart, M. A.M., Muskens, F., Jung, S., Hoogsteden, H. C., Hammad, H., Lambrecht, B. N. (2008). Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells. JEM 205: 869-882 [Abstract] [Full Text]  
• Xu, G., Liu, D., Okwor, I., Wang, Y., Korner, H., Kung, S. K. P., Fu, Y.-X., Uzonna, J. E. (2007). LIGHT Is Critical for IL-12 Production by Dendritic Cells, Optimal CD4+ Th1 Cell Response, and Resistance to Leishmania major. J. Immunol. 179: 6901-6909 [Abstract] [Full Text]  
• Johnson, L. M., Scott, P. (2007). STAT1 Expression in Dendritic Cells, but Not T Cells, Is Required for Immunity to Leishmania major. J. Immunol. 178: 7259-7266 [Abstract] [Full Text]  
• Stober, C. B., Lange, U. G., Roberts, M. T. M., Alcami, A., Blackwell, J. M. (2007). Heterologous Priming-Boosting with DNA and Modified Vaccinia Virus Ankara Expressing Tryparedoxin Peroxidase Promotes Long-Term Memory against Leishmania major in Susceptible BALB/c Mice. Infect. Immun. 75: 852-860 [Abstract] [Full Text]  
• Lou, Y., Liu, C., Kim, G. J., Liu, Y.-J., Hwu, P., Wang, G. (2007). Plasmacytoid Dendritic Cells Synergize with Myeloid Dendritic Cells in the Induction of Antigen-Specific Antitumor Immune Responses. J. Immunol. 178: 1534-1541 [Abstract] [Full Text]  
• Reinhardt, R. L., Hong, S., Kang, S.-J., Wang, Z.-e., Locksley, R. M. (2006). Visualization of IL-12/23p40 In Vivo Reveals Immunostimulatory Dendritic Cell Migrants that Promote Th1 Differentiation. J. Immunol. 177: 1618-1627 [Abstract] [Full Text]  
• Wille-Reece, U., Flynn, B. J., Lore, K., Koup, R. A., Kedl, R. M., Mattapallil, J. J., Weiss, W. R., Roederer, M., Seder, R. A. (2005). HIV Gag protein conjugated to a Toll-like receptor 7/8 agonist improves the magnitude and quality of Th1 and CD8+ T cell responses in nonhuman primates. Proc. Natl. Acad. Sci. USA 102: 15190-15194 [Abstract] [Full Text]  
• Stober, C. B., Lange, U. G., Roberts, M. T. M., Alcami, A., Blackwell, J. M. (2005). IL-10 from Regulatory T Cells Determines Vaccine Efficacy in Murine Leishmania major Infection. J. Immunol. 175: 2517-2524 [Abstract] [Full Text]  
• Wille-Reece, U., Wu, C.-y., Flynn, B. J., Kedl, R. M., Seder, R. A. (2005). Immunization with HIV-1 Gag Protein Conjugated to a TLR7/8 Agonist Results in the Generation of HIV-1 Gag-Specific Th1 and CD8+ T Cell Responses. J. Immunol. 174: 7676-7683 [Abstract] [Full Text]  
• Mason, K. A., Ariga, H., Neal, R., Valdecanas, D., Hunter, N., Krieg, A. M., Whisnant, J. K., Milas, L. (2005). Targeting Toll-like Receptor 9 with CpG Oligodeoxynucleotides Enhances Tumor Response to Fractionated Radiotherapy. Clin. Cancer Res. 11: 361-369 [Abstract] [Full Text]  
• van Mierlo, G. J. D., Boonman, Z. F. H. M., Dumortier, H. M. H., den Boer, A. Th., Fransen, M. F., Nouta, J., van der Voort, E. I. H., Offringa, R., Toes, R. E. M., Melief, C. J. M. (2004). Activation of Dendritic Cells That Cross-Present Tumor-Derived Antigen Licenses CD8+ CTL to Cause Tumor Eradication. J. Immunol. 173: 6753-6759 [Abstract] [Full Text]  
• Schlecht, G., Garcia, S., Escriou, N., Freitas, A. A., Leclerc, C., Dadaglio, G. (2004). Murine plasmacytoid dendritic cells induce effector/memory CD8+ T-cell responses in vivo after viral stimulation. Blood 104: 1808-1815 [Abstract] [Full Text]  
• Pinto, E. F., Pinheiro, R. O., Rayol, A., Larraga, V., Rossi-Bergmann, B. (2004). Intranasal Vaccination against Cutaneous Leishmaniasis with a Particulated Leishmanial Antigen or DNA Encoding LACK. Infect. Immun. 72: 4521-4527 [Abstract] [Full Text]  
• Lange, U. G., Mastroeni, P., Blackwell, J. M., Stober, C. B. (2004). DNA-Salmonella enterica Serovar Typhimurium Primer-Booster Vaccination Biases towards T Helper 1 Responses and Enhances Protection against Leishmania major Infection in Mice. Infect. Immun. 72: 4924-4928 [Abstract] [Full Text]  
• Darrah, P. A., Monaco, M. C. G., Jain, S., Hondalus, M. K., Golenbock, D. T., Mosser, D. M. (2004). Innate Immune Responses to Rhodococcus equi. J. Immunol. 173: 1914-1924 [Abstract] [Full Text]  
• Anderson, C. F., Lucas, M., Gutierrez-Kobeh, L., Field, A. E., Mosser, D. M. (2004). T Cell Biasing by Activated Dendritic Cells. J. Immunol. 173: 955-961 [Abstract] [Full Text]  
• Fujii, S.-i., Liu, K., Smith, C., Bonito, A. J., Steinman, R. M. (2004). The Linkage of Innate to Adaptive Immunity via Maturing Dendritic Cells In Vivo Requires CD40 Ligation in Addition to Antigen Presentation and CD80/86 Costimulation. JEM 199: 1607-1618 [Abstract] [Full Text]  
• Ramirez-Pineda, J. R., Frohlich, A., Berberich, C., Moll, H. (2004). Dendritic Cells (DC) Activated by CpG DNA Ex Vivo Are Potent Inducers of Host Resistance to an Intracellular Pathogen That Is Independent of IL-12 Derived from the Immunizing DC. J. Immunol. 172: 6281-6289 [Abstract] [Full Text]  
• Salio, M., Palmowski, M. J., Atzberger, A., Hermans, I. F., Cerundolo, V. (2004). CpG-matured Murine Plasmacytoid Dendritic Cells Are Capable of In Vivo Priming of Functional CD8 T Cell Responses to Endogenous but Not Exogenous Antigens. JEM 199: 567-579 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS