CpG oligodeoxynucleotides induce Ca2+-dependent phospholipase D activity leading to phagolysosome maturation and intracellular mycobacterial growth inhibition in monocytes.
Synthetic oligodeoxynucleotides containing CpG motifs (CpG ODN) have been reported to induce antimycobacterial activity both in vitro and in vivo. The present study analyzes the signals leading to CpG ODN-induced antimicrobial activity in monocytes. In this context, CpG, but not GpC, ODN induced cytosolic Ca2+ influx of extracellular origin which, in turn, activated host phospholipase D (PLD). The production of CpG-induced PLD-dependent phosphatidic acid induced the maturation of phagolysosomes and intracellular mycobacterial growth inhibition. These results show the presence of an antimicrobial pathway in monocytes, mediated by Ca2+-dependent PLD which can be useful for the exploitation of novel anti-tuberculosis immunotherapy approaches.
Greco
Emanuela
E
Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
De Spirito
Marco
M
Papi
Massimiliano
M
Fossati
Marco
M
Auricchio
Giovanni
G
Fraziano
Maurizio
M
D002118:Calcium / Q000502:physiology; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000502:physiology; D004789:Enzyme Activation; D006801:Humans; D009000:Monocytes / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D010588:Phagosomes / Q000502:physiology*; D010739:Phospholipase D / Q000502:physiology*
C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D010739:Phospholipase D; D002118:Calcium