IFN-GAMMA PRIMES MACROPHAGE RESPONSES TO BACTERIAL-DNA

Macrophages recognize and are activated by unmethylated CpG motifs in bacterial DNA, Here we demonstrate that production of nitric oxide (NO ) from murine RAW 264 macrophages and bone marrow-derived macrophages (BMM) in response to bacterial DNA is absolutely dependent on interfer on-gamma (IFN-gamma) priming. Similarly, arginine uptake and expressio n of the inducible nitric oxide synthase (iNOS) gene in response to ba cterial DNA in BMM occurred only after IFN-gamma priming, In contrast, mRNA for the cationic amino acid transporter, CAT2, was induced by pl asmid DNA alone, and priming with IFN-gamma had no effect on this resp onse. Tumor necrosis factor-alpha (TNF-alpha) release from RAW 264 and BMM in response to bacterial DNA was augmented by IFN-gamma pretreatm ent, In a stably transfected HIV-1 long terminal repeat (LTR) lucifera se RAW 264 cell line, IFN-gamma and bacterial DNA synergized in activa tion of the HIV-1 LTR. Bacterial DNA has been shown to induce IFN-gamm a production in vivo as an indirect consequence of interleukin-12 (IL- 12) and TNF-alpha production from macrophages, The results herein sugg est the existence of a self-amplifying loop that may have implications for therapeutic applications of bacterial DNA.