Research

CpG oligonucleotide activates Toll-like receptor 9 and causes lung inflammation in vivo

Pascal Knuefermann^1* , Georg Baumgarten^1* , Alexander Koch² , Markus Schwederski¹ , Markus Velten¹ , Heidi Ehrentraut¹ , Jan Mersmann³ , Rainer Meyer⁴ , Andreas Hoeft¹ , Kai Zacharowski² and Christian Grohé⁵

¹  Department for Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53125 Bonn, Germany

²  Molecular Cardioprotection & Inflammation Group, Department of Anesthesia, Bristol Royal Infirmary, Bristol BS2 8HW, UK

³  Molecular Cardioprotection & Inflammation Group, Department of Anesthesia, University Hospital Düsseldorf, Moorenstrasse 5, 40225 Düsseldorf, Germany

⁴  Institute of Physiology II, University Hospital Bonn, Wilhelmstrasse 31, 53111 Bonn, Germany

⁵  Department of Internal Medicine, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53125 Bonn, Germany

author email corresponding author email* Contributed equally

Respiratory Research 2007, 8:72doi:10.1186/1465-9921-8-72

Published:	9 October 2007

Abstract

Background

Bacterial DNA containing motifs of unmethylated CpG dinucleotides (CpG-ODN) initiate an innate immune response mediated by the pattern recognition receptor Toll-like receptor 9 (TLR9). This leads in particular to the expression of proinflammatory mediators such as tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β). TLR9 is expressed in human and murine pulmonary tissue and induction of proinflammatory mediators has been linked to the development of acute lung injury. Therefore, the hypothesis was tested whether CpG-ODN administration induces an inflammatory response in the lung via TLR9 in vivo.

Methods

Wild-type (WT) and TLR9-deficient (TLR9-D) mice received CpG-ODN intraperitoneally (1668-Thioat, 1 nmol/g BW) and were observed for up to 6 hrs. Lung tissue and plasma samples were taken and various inflammatory markers were measured.

Results

In WT mice, CpG-ODN induced a strong activation of pulmonary NFκB as well as a significant increase in pulmonary TNF-α and IL-1β mRNA/protein. In addition, cytokine serum levels were significantly elevated in WT mice. Increased pulmonary content of lung myeloperoxidase (MPO) was documented in WT mice following application of CpG-ODN. Bronchoalveolar lavage (BAL) revealed that CpG-ODN stimulation significantly increased total cell number as well as neutrophil count in WT animals. In contrast, the CpG-ODN-induced inflammatory response was abolished in TLR9-D mice.

Conclusion

This study suggests that bacterial CpG-ODN causes lung inflammation via TLR9.