Impaired Toll-like Receptor 9 Expression in Alveolar Macrophages with No Sensitivity to CpG DNA

Abstract

Unmethylated CpG motifs in bacterial DNA or synthetic oligodeoxynucleotides (ODN) potently stimulate the innate immune system, and they are recognized by Toll-like receptor 9 (TLR9), which is expressed by monocytes/macrophages, dendritic cells, and B cells. However, it is unknown whether alveolar macrophages (AMs) express functional TLR9. To clarify this, we analyzed mRNA expressions of TLRs in murine AMs by real-time polymerase chain reaction, and compared with those in other tissue macrophages and lung antigen-presenting cells. In addition, we determined the sensitivity of these cell populations to CpG-ODN. Interestingly, TLR9 mRNA was almost absent in AMs, but highly expressed in bone marrow-derived macrophages and peritoneal macrophages, whereas TLR2 and TLR4 were present in all macrophage populations. Consistent with the receptor expression, AMs showed no sensitivity to CpG-ODN, whereas other macrophage populations secreted tumor necrosis factor alpha, interleukin 12 p40, and interleukin 6, and enhanced expression of CD40, CD80, and CD86, in response to CpG-ODN. Lung dendritic cells and B cells highly expressed TLR9 mRNA and responded to CpG-ODN. These results indicate selective loss of TLR9 expression in AMs with no sensitivity to CpG-ODN, suggesting that dendritic cells and B cells play a role in the immune response against bacterial DNA in the lung.