title: 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.
authors.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Takafumi
authors.initials: T
authors.lastname: Suda
authors.forename: Tateaki
authors.initials: T
authors.lastname: Naito
authors.forename: Kyotaro
authors.initials: K
authors.lastname: Ide
authors.forename: Kingo
authors.initials: K
authors.lastname: Chida
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D007156:Immunologic Memory; D016676:Macrophages, Alveolar / Q000166:cytology* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D012143:Respiratory Physiological Phenomena; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D051217:Toll-Like Receptor 9
chemical_list: C408982:CPG-oligonucleotide; D016207:Cytokines; D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9