Abstract
Unmethylated CpG motifs frequently appear in bacterial DNA and induce immune responses through Toll-like receptor 9 (TLR9) pathway. Noble class of suppressive oligodeoxynucleotide (suppressive ODN) inhibits the immune activation by CpG DNAs. Interleukin-12 (IL-12) has several biological activities and modulates inflammatory responses in the lungs. Objectives: The objective of this study was to show that bacterial DNA induces IL-12 expression through TLR9 pathway in vivo. Methods: To test IL-12 production by bacterial DNA in the lungs, bacterial DNA (E. coli DNA) or mammalian DNA (calf thymus DNA) was intratracheally instilled into the murine lungs. 16 hours after instillation, bronchoalveolar lavage (BAL) was performed. Recovered BAL fluid were stored and examined for IL-12 concentration by ELISA. Results: E. coli DNA but not calf thymus DNA induced IL-12 production. Oligodeoxynucleotide containing unmethylated CpG motifs (CpG ODN) also induced IL-12 production. Neutral ODN which does not contain CpG motif did not induce IL-12 production. Suppressive ODN significantly inhibited IL-12 production by E. coli DNA and CpG ODN. Conclusions: This in vivo study demonstrated that bacterial DNA induces IL-12 production through TLR9-dependent pathway.
