| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,§,§
Departments of
*
Medicine,
Pathology, and
Microbiology, University of Texas Health Science Center, San Antonio, TX 78284;
§
South Texas Veterans Health Care System, Audie L. Murphy Division, San Antonio, TX 78284; and
¶
Infectious Diseases Service, Department of Medicine, Wilford Hall Medical Center, Lackland Air Force Base, TX 78236
Infections with intracellular pathogens such as Leishmania
donovani and Mycobacterium tuberculosis pose
serious health problems worldwide. Effective vaccines for these
pathogens are not available. Furthermore, despite optimal therapy,
disease progression is often seen with several intracellular
infections. For these reasons, we initiated studies to develop novel
anti-infective vaccine and treatment strategies that couple the
potent Ag-presenting capacity of dendritic cells (DC) with paracrine
delivery of potent anti-infective cytokines such as IL-12 to local
immune response sites. We tested this strategy in a murine model of
visceral leishmaniasis. Adoptive transfer of DCs pulsed ex vivo with
soluble L. donovani Ags (SLDA) to naive mice induced the
Ag-specific production of IFN-
, and increased the percentage of
activation markers on spleen lymphocytes. SLDA-pulsed DCs engineered by
retroviral gene transfer techniques to secrete high levels of
biologically active murine IL-12 augmented this immune response
further. In several different vaccination and immunotherapy protocols,
compared with sham-treated mice, animals receiving SLDA-pulsed DCs
either before or following infection had 1–3 log lower parasite
burdens, and this protection was associated with a pronounced
enhancement in the parasite-specific IFN- response. The augmentation
of this protection by IL-12-engineered DCs was striking. First, live
parasites were not detected in the liver of mice vaccinated with
IL-12-transduced, SLDA-pulsed DCs. Second, this parasitological
response was associated with a nearly normal liver histology. In
contrast, parasites and granulomas were found in mice vaccinated with
SLDA-pulsed, nontransduced DCs. Collectively, these studies provide the
rationale for the development of potent DC-based
immunotherapies.
This article has been cited by other articles:
|
|
 |
|
  S. McCormick, M. Santosuosso, C.-L. Small, C. R. Shaler, X. Zhang, M. Jeyanathan, J. Mu, S. Takenaka, P. Ngai, J. Gauldie, et al. Mucosally Delivered Dendritic Cells Activate T Cells Independently of IL-12 and Endogenous APCs J. Immunol., August 15, 2008; 181(4): 2356 - 2367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Basu, S. Bhaumik, A. K. Haldar, K. Naskar, T. De, S. K. Dana, P. Walden, and S. Roy Hybrid Cell Vaccination Resolves Leishmania donovani Infection by Eliciting a Strong CD8+ Cytotoxic T-Lymphocyte Response with Concomitant Suppression of Interleukin-10 (IL-10) but Not IL-4 or IL-13 Infect. Immun., December 1, 2007; 75(12): 5956 - 5966. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Maurer, S. L. Kostka, F. Siebenhaar, K. Moelle, M. Metz, J. Knop, and E. von Stebut Skin mast cells control T cell-dependent host defense in Leishmania major infections FASEB J, December 1, 2006; 20(14): 2460 - 2467. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Woelbing, S. L. Kostka, K. Moelle, Y. Belkaid, C. Sunderkoetter, S. Verbeek, A. Waisman, A. P. Nigg, J. Knop, M. C. Udey, et al. Uptake of Leishmania major by dendritic cells is mediated by Fc{gamma} receptors and facilitates acquisition of protective immunity J. Exp. Med., January 23, 2006; 203(1): 177 - 188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Buettner, C. Meinken, M. Bastian, R. Bhat, E. Stossel, G. Faller, G. Cianciolo, J. Ficker, M. Wagner, M. Rollinghoff, et al. Inverse Correlation of Maturity and Antibacterial Activity in Human Dendritic Cells J. Immunol., April 1, 2005; 174(7): 4203 - 4209. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kuipers, C. Heirman, D. Hijdra, F. Muskens, M. Willart, S. van Meirvenne, K. Thielemans, H. C. Hoogsteden, and B. N. Lambrecht Dendritic cells retrovirally overexpressing IL-12 induce strong Th1 responses to inhaled antigen in the lung but fail to revert established Th2 sensitization J. Leukoc. Biol., November 1, 2004; 76(5): 1028 - 1038. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ghosh, C. Pal, M. Ray, S. Maitra, L. Mandal, and S. Bandyopadhyay Dendritic Cell-Based Immunotherapy Combined with Antimony-Based Chemotherapy Cures Established Murine Visceral Leishmaniasis J. Immunol., June 1, 2003; 170(11): 5625 - 5629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Nakamura, T. Suda, T. Nagata, T. Aoshi, M. Uchijima, A. Yoshida, K. Chida, Y. Koide, and H. Nakamura Induction of Protective Immunity to Listeria monocytogenes with Dendritic Cells Retrovirally Transduced with a Cytotoxic T Lymphocyte Epitope Minigene Infect. Immun., April 1, 2003; 71(4): 1748 - 1754. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. A. Ansari, A. E. Mayne, J. B. Sundstrom, P. Bostik, B. Grimm, J. D. Altman, and F. Villinger Administration of Recombinant Rhesus Interleukin-12 during Acute Simian Immunodeficiency Virus (SIV) Infection Leads to Decreased Viral Loads Associated with Prolonged Survival in SIVmac251-Infected Rhesus Macaques J. Virol., February 15, 2002; 76(4): 1731 - 1743. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. Lipscomb and B. J. Masten Dendritic Cells: Immune Regulators in Health and Disease Physiol Rev, January 1, 2002; 82(1): 97 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. W. Murray Clinical and Experimental Advances in Treatment of Visceral Leishmaniasis Antimicrob. Agents Chemother., August 1, 2001; 45(8): 2185 - 2197. [Full Text] [PDF]
|
|
|
|
 |
|
 E. Handman Leishmaniasis: Current Status of Vaccine Development Clin. Microbiol. Rev., April 1, 2001; 14(2): 229 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Demangel, U. Palendira, C. G. Feng, A. W. Heath, A. G. D. Bean, and W. J. Britton Stimulation of Dendritic Cells via CD40 Enhances Immune Responses to Mycobacterium tuberculosis Infection Infect. Immun., April 1, 2001; 69(4): 2456 - 2461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Stager, D. F. Smith, and P. M. Kaye Immunization with a Recombinant Stage-Regulated Surface Protein from Leishmania donovani Induces Protection Against Visceral Leishmaniasis J. Immunol., December 15, 2000; 165(12): 7064 - 7071. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. Melby, G. B. Ogden, H. A. Flores, W. Zhao, C. Geldmacher, N. M. Biediger, S. K. Ahuja, J. Uranga, and M. Melendez Identification of Vaccine Candidates for Experimental Visceral Leishmaniasis by Immunization with Sequential Fractions of a cDNA Expression Library Infect. Immun., October 1, 2000; 68(10): 5595 - 5602. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Quinones, S. K. Ahuja, P. C. Melby, L. Pate, R. L. Reddick, and S. S. Ahuja Preformed Membrane-associated Stores of Interleukin (IL)-12 Are a Previously Unrecognized Source of Bioactive IL-12 That Is Mobilized within Minutes of Contact with an Intracellular Parasite J. Exp. Med., August 14, 2000; 192(4): 507 - 516. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Sato, S. K. Ahuja, M. Quinones, V. Kostecki, R. L. Reddick, P. C. Melby, W. A. Kuziel, and S. S. Ahuja CC Chemokine Receptor (CCR)2 Is Required for Langerhans Cell Migration and Localization of T Helper Cell Type 1 (Th1)-inducing Dendritic Cells: Absence of CCR2 Shifts the Leishmania major-resistant Phenotype to a Susceptible State Dominated by Th2 Cytokines, B Cell Outgrowth, and Sustained Neutrophilic Inflammation J. Exp. Med., July 10, 2000; 192(2): 205 - 218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Sato, W. A. Kuziel, P. C. Melby, R. L. Reddick, V. Kostecki, W. Zhao, N. Maeda, S. K. Ahuja, and S. S. Ahuja Defects in the Generation of IFN-{gamma} Are Overcome to Control Infection with Leishmania donovani in CC Chemokine Receptor (CCR) 5-, Macrophage Inflammatory Protein-1{alpha}-, or CCR2-Deficient Mice J. Immunol., November 15, 1999; 163(10): 5519 - 5525. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
