PMID- 12438324
OWN - NLM
STAT- MEDLINE
DCOM- 20030107
LR  - 20220216
IS  - 0019-9567 (Print)
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Linking)
VI  - 70
IP  - 12
DP  - 2002 Dec
TI  - Mycobacterium bovis BCG producing interleukin-18 increases antigen-specific gamma 
      interferon production in mice.
PG  - 6549-57
AB  - Interleukin-18 (IL-18) and IL-12 play a critical role in the expression of 
      cell-mediated immunity involved in host defense against intracellular pathogens. 
      Both cytokines are produced by macrophages and act in synergy to induce gamma 
      interferon (IFN-gamma) production by T, B, and natural killer cells. In the 
      present study, we analyzed both cellular and humoral responses upon infection 
      with IL-18-secreting BCG of BALB/c and C3H/HeJ mice, two strains known to differ 
      in their ability to support the growth of BCG. The cDNA encoding mature IL-18 was 
      fused in frame with the alpha-antigen signal peptide-coding sequence, cloned 
      downstream of the mycobacterial hsp60 promoter and expressed in BCG. IL-18 
      produced by the recombinant BCG strain was functional, as judged by 
      NF-kappaB-mediated luciferase induction in a tissue culture assay. When 
      susceptible mice were infected with IL-18-producing BCG, their splenocytes were 
      found to produce higher amounts of Th1 cytokines after stimulation with 
      mycobacterial antigens than the splenocytes of mice infected with the 
      nonrecombinant BCG. This was most prominent for IFN-gamma, although the 
      mycobacterial antigen-specific secretion of granulocyte-macrophage 
      colony-stimulating factor and IL-10 was also augmented after infection with the 
      recombinant BCG compared to infection with nonrecombinant BCG. In contrast, the 
      immunoglobulin G levels in serum against mycobacterial antigens were lower when 
      the mice were infected with IL-18-producing BCG compared to infection with 
      nonrecombinant BCG. The IL-18 effect was delayed in BALB/c compared to C3H/HeJ 
      mice. These results indicate that the production of IL-18 by recombinant BCG may 
      enhance the immunomodulatory properties of BCG further toward a Th1 profile. This 
      may be particularly useful for immunotherapeutic or prophylactic interventions in 
      which a Th1 response is most desirable.
FAU - Biet, Franck
AU  - Biet F
AD  - Laboratoire de Microbiologie Genetique et Moleculaire, INSERM U447, Institut 
      Pasteur de Lille, France.
FAU - Kremer, Laurent
AU  - Kremer L
FAU - Wolowczuk, Isabelle
AU  - Wolowczuk I
FAU - Delacre, Myriam
AU  - Delacre M
FAU - Locht, Camille
AU  - Locht C
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Antibodies, Bacterial)
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Interleukin-18)
RN  - 0 (Recombinant Proteins)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Antibodies, Bacterial/blood
MH  - Antigens, Bacterial/immunology
MH  - Female
MH  - Humans
MH  - Immunization
MH  - Interferon-gamma/*biosynthesis
MH  - Interleukin-18/*biosynthesis/genetics
MH  - Lymphocyte Activation
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C3H
MH  - Mycobacterium bovis/*genetics/*immunology/pathogenicity
MH  - Recombinant Proteins/immunology/metabolism
MH  - Th1 Cells/immunology
MH  - Transfection
MH  - Tuberculosis/*immunology/microbiology
MH  - U937 Cells
PMC - PMC132979
EDAT- 2002/11/20 04:00
MHDA- 2003/01/08 04:00
CRDT- 2002/11/20 04:00
PHST- 2002/11/20 04:00 [pubmed]
PHST- 2003/01/08 04:00 [medline]
PHST- 2002/11/20 04:00 [entrez]
AID - 0536 [pii]
AID - 10.1128/IAI.70.12.6549-6557.2002 [doi]
PST - ppublish
SO  - Infect Immun. 2002 Dec;70(12):6549-57. doi: 10.1128/IAI.70.12.6549-6557.2002.