| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Institute for Molecular Biology of Infectious Diseases, University of Würzburg, Würzburg, Germany;
Institute of Immunology, College of Veterinary Medicine, University of Leipzig, Leipzig, Germany; and
Corixa, Seattle, WA 98104
Upon loading with microbial Ag and adoptive transfer, dendritic cells (DC) are able to induce immunity to infections. This offers encouragement for the development of DC-based vaccination strategies. However, the mechanisms underlying the adjuvant effect of DC are not fully understood, and there is a need to identify Ag with which to arm DC. In the present study, we analyzed the role of DC-derived IL-12 in the induction of resistance to Leishmania major, and we evaluated the protective efficacy of DC loaded with individual Leishmania Ag. Using Ag-pulsed Langerhans cells (LC) from IL-12-deficient or wild-type mice for immunization of susceptible animals, we showed that the inability to release IL-12 completely abrogated the capacity of LC to mediate protection against leishmaniasis. This suggests that the availability of donor LC-derived IL-12 is a requirement for the development of protective immunity. In addition, we tested the protective effect of LC loaded with Leishmania homolog of receptor for activated C kinase, gp63, promastigote surface Ag, kinetoplastid membrane protein-11, or Leishmania homolog of eukaryotic ribosomal elongation and initiation factor 4a. The results show that mice vaccinated with LC that had been pulsed with selected molecularly defined parasite proteins are capable of controlling infection with L. major. Moreover, the protective potential of DC pulsed with a given Leishmania Ag correlated with the level of their IL-12 expression. Analysis of the cytokine profile of mice after DC-based vaccination revealed that protection was associated with a shift toward a Th1-type response. Together, these findings emphasize the critical role of IL-12 produced by the sensitizing DC and suggest that the development of a DC-based subunit vaccine is feasible.
This article has been cited by other articles:
|
|
 |
|
  F. Hkima Abou Fakher, N. Rachinel, M. Klimczak, J. Louis, and N. Doyen TLR9-Dependent Activation of Dendritic Cells by DNA from Leishmania major Favors Th1 Cell Development and the Resolution of Lesions J. Immunol., February 1, 2009; 182(3): 1386 - 1396. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Soong Modulation of Dendritic Cell Function by Leishmania Parasites J. Immunol., April 1, 2008; 180(7): 4355 - 4360. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. F. Tuon, V. S. Amato, H. A. Bacha, T. AlMusawi, M. I. Duarte, and V. Amato Neto Toll-Like Receptors and Leishmaniasis Infect. Immun., March 1, 2008; 76(3): 866 - 872. [Full Text] [PDF]
|
|
|
|
|
|
R. N. Coler, Y. Goto, L. Bogatzki, V. Raman, and S. G. Reed Leish-111f, a Recombinant Polyprotein Vaccine That Protects against Visceral Leishmaniasis by Elicitation of CD4+ T Cells Infect. Immun., September 1, 2007; 75(9): 4648 - 4654. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Schleicher, J. Liese, I. Knippertz, C. Kurzmann, A. Hesse, A. Heit, J. A.A. Fischer, S. Weiss, U. Kalinke, S. Kunz, et al. NK cell activation in visceral leishmaniasis requires TLR9, myeloid DCs, and IL-12, but is independent of plasmacytoid DCs J. Exp. Med., April 16, 2007; 204(4): 893 - 906. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Yu, H. Huang, J. Xiang, L. A. Babiuk, and S. van Drunen Littel-van den Hurk Dendritic cells pulsed with hepatitis C virus NS3 protein induce immune responses and protection from infection with recombinant vaccinia virus expressing NS3 J. Gen. Virol., January 1, 2006; 87(1): 1 - 10. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kodali, W. Ding, J. Huang, K. Seiffert, J. A. Wagner, and R. D. Granstein Vasoactive Intestinal Peptide Modulates Langerhans Cell Immune Function J. Immunol., November 15, 2004; 173(10): 6082 - 6088. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. F. Vanloubbeeck, A. E. Ramer, F. Jie, and D. E. Jones CD4+ Th1 Cells Induced by Dendritic Cell-Based Immunotherapy in Mice Chronically Infected with Leishmania amazonensis Do Not Promote Healing Infect. Immun., August 1, 2004; 72(8): 4455 - 4463. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Ramirez-Pineda, A. Frohlich, C. Berberich, and H. Moll 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., May 15, 2004; 172(10): 6281 - 6289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Shah, P. A. Darrah, D. R. Ambrozak, T. N. Turon, S. Mendez, J. Kirman, C.-Y. Wu, N. Glaichenhaus, and R. A. Seder Dendritic Cells Are Responsible for the Capacity of CpG Oligodeoxynucleotides to Act as an Adjuvant for Protective Vaccine Immunity Against Leishmania major in Mice J. Exp. Med., July 21, 2003; 198(2): 281 - 291. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
