This Article Full Text (PDF) Other Versions of this Article: IAI.00322-07v1 75/11/5368    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Triccas, J. A. Articles by Britton, W. J. Search for Related Content PubMed PubMed Citation Articles by Triccas, J. A. Articles by Britton, W. J.

 Previous Article  |  Next Article 

Infect. Immun. doi:10.1128/IAI.00322-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Effects of DNA- and BCG-based delivery of Flt3 ligand on protective immunity to Mycobacterium tuberculosis

Microbial Pathogenesis and Immunity Group, Discipline of Infectious Diseases and Immunology, Discipline of Medicine and Centenary Institute of Cancer Medicine and Cell Biology, University of Sydney, Australia

^* To whom correspondence should be addressed. Email: jamiet{at}infdis.usyd.edu.au.

	Abstract

The control of intracellular pathogens such as Mycobacterium tuberculosis is dependant on the activation and maintenance of pathogen-reactive T cells. Dendritic cells (DCs) are the major antigen presenting cells (APCs) initiating anti-mycobacterial T cell responses in vivo. To investigate if immunization strategies that aim to optimize DC function can improve protective immunity against virulent mycobacterial infection, we have exploited the ability of the hematopoietic growth factor Flt3 ligand (Flt3L) to expand DC number in vivo. A DNA fusion of the gene encoding murine Flt3L and M. tuberculosis Ag85B stimulated enhanced IFN- release by T cells and provided superior protection against virulent M. tuberculosis than DNA encoding the single components. Vaccination of mice with a recombinant BCG strain secreting Flt3L (BCG:Flt3L) led to an early expansion of DCs, compared to immunization with BCG alone, and this effect was associated with increased stimulation of BCG-reactive IFN--secreting T cells. Both BCG and BCG:Flt3L provided similar protective efficacy against low-dose aerosol M. tuberculosis, however immunization of immunodeficient mice revealed that BCG:Flt3L was markedly less virulent than conventional BCG. These results demonstrate the potential of in vivo targeting of DCs to improve anti-mycobacterial vaccine efficacy.