CpG oligonucleotides partially inhibit growth of Mycobacterium tuberculosis, but not Salmonella or Listeria, in human monocyte-derived macrophages.
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.
Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA. jennifer.wang@umassmed.edu
Jennifer P
JP
Wang
Tomoko
T
Hayashi
Sandip K
SK
Datta
Richard S
RS
Kornbluth
Eyal
E
Raz
Donald G
DG
Guiney
D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology*; D001483:Base Sequence; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D008089:Listeria monocytogenes / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000494:pharmacology*; D011994:Recombinant Proteins; D019779:Salmonella enterica / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity; D013045:Species Specificity; D014774:Virulence
D000995:Antitubercular Agents; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D007371:Interferon-gamma