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TLR9‐independent effects of inhibitory oligonucleotides on macrophage responses to S. typhimurium
Author(s) -
Trieu Angela,
Bokil Nilesh,
Dunn Jasmyn A,
Roberts Tara L,
Xu Damo,
Liew Foo Y,
Hume David A,
Stacey Katryn J,
Sweet Matthew J
Publication year - 2008
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2008.95
Subject(s) - tlr9 , toll like receptor 9 , biology , tlr2 , salmonella enterica , innate immune system , microbiology and biotechnology , immune system , oligonucleotide , cpg site , intracellular , cpg oligodeoxynucleotide , dna , salmonella , gene , gene expression , immunology , bacteria , dna methylation , genetics
Detection of bacterial CpG‐containing DNA (CpG DNA) by innate immune cells is dependent on toll‐like receptor 9 (TLR9). Here we show that the expression of tlr 9 mRNA was induced in mouse bone marrow‐derived macrophages (BMMs) upon infection with the facultative Gram‐negative intracellular bacterium Salmonella enterica serovar Typhimurium (S. typhimurium) . Treatment of BMM with the inhibitory oligonucleotide (ODN) 2114, an antagonist of TLR9 signalling, enhanced intracellular S. typhimurium numbers approximately fivefold, whereas a control ODN (2310) had no significant effect. Surprisingly, 2114 also amplified S. typhimurium bacterial loads in TLR9‐deficient BMM. Indeed, 2114 suppressed responses (nuclear factor‐κB‐dependent reporter gene expression and interleukin‐12p40 secretion) to not only CpG DNA, but also the TLR2 ligand Pam 3 Cys, in BMM and RAW264 cells in a sequence‐specific manner. Inhibitory ODNs, which have been proposed as therapeutic agents for the treatment of systemic lupus erythematosus because of their inhibitory effects on TLR9 signalling, may thus compromise the host response to bacterial pathogens through TLR9‐independent mechanisms.