Role of bacterial DNA in macrophage activation by group B streptococci

Ajay Talati, Hae Jong Kim, Young In Kim, Ae-Kyung Yi, B. Keith English

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Abstract

Bacterial DNA (CpG DNA) induces macrophage activation and the production of inflammatory mediators, including tumor necrosis factor (TNF) and nitric oxide (NO) by these cells. However, the role of bacterial DNA in the macrophage response to whole bacteria is unknown. We used overlapping strategies to estimate the relative contribution of bacterial DNA to the upregulation of TNF and NO production in macrophages stimulated with antibiotic-treated group B streptococci (GBS). Selective inhibitors of the bacterial DNA/TLR9 pathway (chloroquine, an inhibitory oligonucleotide, and DNase I) consistently inhibited GBS-induced TNF secretion by 35-50% in RAW 264.7 macrophages and murine splenic macrophages, but had no effect on inducible nitric oxide synthase (iNOS) accumulation or NO secretion. Similarly, splenic and peritoneal macrophages from mice lacking TLR9 expression secreted 40% less TNF than macrophages from control mice after GBS challenge but accumulated comparable amounts of iNOS protein. Finally, studies in both RAW 264.7 cells and macrophages from TLR9-/- mice implicated GBS DNA in the upregulation of interleukins 6 (IL-6) and 12 (IL-12) but not interferon-beta (IFNβ), a key intermediary in macrophage production of iNOS/NO. Our data suggest that the bacterial DNA/TLR9 pathway plays an important role in stimulating TNF rather than NO production in macrophages exposed to antibiotic-treated GBS, and that TLR9-independent upregulation of IFNβ production by whole GBS may account for this difference.

Original languageEnglish (US)
Pages (from-to)1106-1113
Number of pages8
JournalMicrobes and Infection
Volume10
Issue number10-11
DOIs
StatePublished - Aug 1 2008

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Bacterial DNA
Streptococcus agalactiae
Macrophage Activation
Macrophages
Nitric Oxide
Tumor Necrosis Factor-alpha
Nitric Oxide Synthase Type II
Up-Regulation
Interferon-beta
Anti-Bacterial Agents
Deoxyribonuclease I
DNA
Chloroquine
Peritoneal Macrophages
Interleukin-12
Oligonucleotides
Interleukin-6
Bacteria

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Role of bacterial DNA in macrophage activation by group B streptococci. / Talati, Ajay; Kim, Hae Jong; Kim, Young In; Yi, Ae-Kyung; English, B. Keith.

In: Microbes and Infection, Vol. 10, No. 10-11, 01.08.2008, p. 1106-1113.

Research output: Contribution to journalArticle

Talati, Ajay ; Kim, Hae Jong ; Kim, Young In ; Yi, Ae-Kyung ; English, B. Keith. / Role of bacterial DNA in macrophage activation by group B streptococci. In: Microbes and Infection. 2008 ; Vol. 10, No. 10-11. pp. 1106-1113.
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