PMID- 17724075
OWN - NLM
STAT- MEDLINE
DCOM- 20071129
LR  - 20181113
IS  - 0019-9567 (Print)
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Linking)
VI  - 75
IP  - 11
DP  - 2007 Nov
TI  - Effects of DNA- and Mycobacterium bovis BCG-based delivery of the Flt3 ligand on 
      protective immunity to Mycobacterium tuberculosis.
PG  - 5368-75
AB  - The control of intracellular pathogens such as Mycobacterium tuberculosis is 
      dependent on the activation and maintenance of pathogen-reactive T cells. 
      Dendritic cells (DCs) are the major antigen-presenting cells initiating 
      antimycobacterial 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 exploited the ability of the 
      hematopoietic growth factor Fms-like tyrosine kinase 3 ligand (Flt3L) to expand 
      the number of DCs in vivo. A DNA fusion of the genes encoding murine Flt3L and M. 
      tuberculosis antigen 85B stimulated enhanced gamma interferon (IFN-gamma) release 
      by T cells and provided better protection against virulent M. tuberculosis than 
      DNA encoding the single components. Vaccination of mice with a recombinant 
      Mycobacterium bovis BCG strain secreting Flt3L (BCG:Flt3L) led to early expansion 
      of DCs compared to immunization with BCG alone, and this effect was associated 
      with increased stimulation of BCG-reactive IFN-gamma-secreting T cells. BCG and 
      BCG:Flt3L provided similar protective efficacies 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 
      antimycobacterial vaccine efficacy.
FAU - Triccas, James A
AU  - Triccas JA
AD  - Microbial Pathogenesis and Immunity Group, Discipline of Infectious Diseases and 
      Immunology, University of Sydney, Sydney, Australia. jamiet@infdis.usyd.edu.au
FAU - Shklovskaya, Elena
AU  - Shklovskaya E
FAU - Spratt, Joanne
AU  - Spratt J
FAU - Ryan, Anthony A
AU  - Ryan AA
FAU - Palendira, Umaimainthan
AU  - Palendira U
FAU - Fazekas de St Groth, Barbara
AU  - Fazekas de St Groth B
FAU - Britton, Warwick J
AU  - Britton WJ
LA  - eng
GR  - HHSN266200400091C/AI/NIAID NIH HHS/United States
GR  - HHSN266200400091C/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070827
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Membrane Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Tuberculosis Vaccines)
RN  - 0 (Vaccines, DNA)
RN  - 0 (Vaccines, Synthetic)
RN  - 0 (flt3 ligand protein)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Antigens, Bacterial/genetics/immunology
MH  - Colony Count, Microbial
MH  - Dendritic Cells/immunology
MH  - Interferon-gamma/biosynthesis
MH  - Lung/microbiology
MH  - Membrane Proteins/genetics/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mycobacterium bovis/genetics/*immunology
MH  - Mycobacterium tuberculosis/*immunology
MH  - Recombinant Fusion Proteins/genetics/immunology
MH  - Spleen/immunology/microbiology
MH  - Survival Analysis
MH  - T-Lymphocytes/immunology
MH  - Tuberculosis/immunology/*prevention & control
MH  - Tuberculosis Vaccines/*immunology
MH  - Vaccines, DNA/genetics/*immunology
MH  - Vaccines, Synthetic/genetics/immunology
PMC - PMC2168302
EDAT- 2007/08/29 09:00
MHDA- 2007/12/06 09:00
PMCR- 2008/03/01
CRDT- 2007/08/29 09:00
PHST- 2007/08/29 09:00 [pubmed]
PHST- 2007/12/06 09:00 [medline]
PHST- 2007/08/29 09:00 [entrez]
PHST- 2008/03/01 00:00 [pmc-release]
AID - IAI.00322-07 [pii]
AID - 0322-07 [pii]
AID - 10.1128/IAI.00322-07 [doi]
PST - ppublish
SO  - Infect Immun. 2007 Nov;75(11):5368-75. doi: 10.1128/IAI.00322-07. Epub 2007 Aug 
      27.