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Published ahead of print on January 7, 2005, doi:10.1164/rccm.200408-1078OC

Am. J. Respir. Crit. Care Med., Volume 171, Number 7, April 2005, 707-713

A more recent version of this article appeared on April 1, 2005
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Submitted on August 20, 2004
Accepted on December 29, 2004

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

Kenichiro Suzuki1, Takafumi Suda1*, Tateaki Naito1, Kyotaro Ide1, Kingo Chida1, and Hirotoshi Nakamura1

1 Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan

* To whom correspondence should be addressed. E-mail: suda{at}hama-med.ac.jp.

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 (DCs), 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 PCR, and compared with those in other tissue macrophages and lung antigen-presenting cells. Additionally, 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 (BMs) and peritoneal macrophages (PMs), whereas TLR2 and TLR4 were present in all macrophage populations. Consistent with the receptor expression, AMs showed no sensitivity to CpG-ODN, while other macrophage populations secreted TNF-{alpha}, IL-12 p40, and IL-6 and enhanced expression of CD40, CD80, and CD86, in response to CpG-ODN. Lung DCs 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 DCs and B cells play a role in the immune response against bacterial DNA in the lung.
Key words: Toll-like receptor 9, alveolar macrophages, dendritic cells




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