Role of CpG ODNs in human macrophages before and after infection with Mycobacterium tuberculosis and their effects in cellular and molecular defence mechanisms

Oligodeoxynucleotides, containing unmethylated CpG dinucleotides within specific sequence contexts in bacterial or viral DNA, are detected as a danger signal by the vertebrate immune system. CpG motifs are sequences with a potent antymycobacterial activity and we tested a panel of eight synthetic CpG ODNs for their capacity to reduce Mycobacterium tuberculosis growth analyzing their effects in vitro in human macrophages. CpG2 ODN is able significantly to reduce pathogen growth while CpG3 ODN determines an enhancement in replication than control macrophages. In term of molecular and cellular mechanisms of defence in the host-pathogen interaction we found a specificity of CpG ODN sequence in intracellular pH decrease but not in Reactive Oxygen Species production, both influenced by CpG. Moreover we analyzed environment of macrophages, stimulated with these two CpG ODNs, before and after infection showing a correlation between mycobacterial growth and IFN- transcription following 1 hour of CpG treatment, and a down-regulation in IFN-mRNA upon pathogen contact. Finally we described a pathway of cytokines, among them SerpinE1 never associated before in M. tuberculosis infection involved in macrophages migration. In conclusion CpG ODNs could be used as vaccine adjuvants confirming their capacities to improve protection against M. tuberculosis involving mechanisms of defence.