Abstract
Immunostimulatory DNA sequences and their synthetic oligonucleotide analogs (CpG-ODN) activate innate immunity and can stimulate antibacterial effects against numerous intracellular pathogens. While it has been shown previously that CpG-ODN inhibit growth of Mycobacterium avium in murine and human macrophages, we now report that Mycobacterium tuberculosis growth can be inhibited by CpG-ODN treatment of human monocyte-derived macrophages (hMDM). This inhibitory effect was reversed by IFN-gamma, which has been shown repeatedly to enhance the growth of virulent M. tuberculosis in cultured hMDM. The antibacterial effect of CpG-ODN in human macrophages was specific for M. tuberculosis when compared to other intracellular pathogens including Listeria monocytogenes and Salmonella enterica serovar Dublin. These data indicate that CpG-ODN can improve the ability of hMDM to contain growth of virulent M. tuberculosis.
MeSH terms
-
Animals
-
Antitubercular Agents / chemistry
-
Antitubercular Agents / pharmacology*
-
Base Sequence
-
Humans
-
Immunity, Innate / drug effects
-
In Vitro Techniques
-
Interferon-gamma / pharmacology
-
Listeria monocytogenes / drug effects*
-
Listeria monocytogenes / growth & development
-
Listeria monocytogenes / immunology
-
Listeria monocytogenes / pathogenicity
-
Macrophages / drug effects*
-
Macrophages / immunology*
-
Macrophages / microbiology
-
Mice
-
Monocytes / drug effects
-
Monocytes / immunology
-
Monocytes / microbiology
-
Mycobacterium tuberculosis / drug effects*
-
Mycobacterium tuberculosis / growth & development
-
Mycobacterium tuberculosis / immunology
-
Mycobacterium tuberculosis / pathogenicity
-
Oligodeoxyribonucleotides / genetics
-
Oligodeoxyribonucleotides / pharmacology*
-
Recombinant Proteins
-
Salmonella enterica / drug effects*
-
Salmonella enterica / growth & development
-
Salmonella enterica / immunology
-
Salmonella enterica / pathogenicity
-
Species Specificity
-
Virulence
Substances
-
Antitubercular Agents
-
CPG-oligonucleotide
-
Oligodeoxyribonucleotides
-
Recombinant Proteins
-
Interferon-gamma