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Infection and Immunity, April 2001, p. 2025-2030, Vol. 69, No. 4
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.4.2025-2030.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Micrococcus luteus Teichuronic Acids Activate Human and Murine Monocytic Cells in a CD14- and Toll-Like Receptor 4-Dependent Manner

Shuhua Yang,1 Shunji Sugawara,1 Toshihiko Monodane,2 Masahiro Nishijima,3 Yoshiyuki Adachi,4 Sachiko Akashi,5 Kensuke Miyake,5 Sumihiro Hase,6 and Haruhiko Takada1,*

Department of Microbiology and Immunology, Tohoku University School of Dentistry, Aoba-ku, Sendai, 980-8575,1 Department of Microbiology and Immunology, Kagoshima University Dental School, Kagoshima, 890-8544,2 Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 152-8640,3 Laboratory of Immunopharmacology of Microbial Products, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo 192-0392,4 Department of Immunology, Saga Medical School, Saga 849-8501,5 and Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka 560-0043,6 Japan

Received 25 September 2000/Returned for modification 19 October 2000/Accepted 28 December 2000

Teichuronic acid (TUA), a component of the cell walls of the gram-positive organism Micrococcus luteus (formerly Micrococcus lysodeikticus), induced inflammatory cytokines in C3H/HeN mice but not in lipopolysaccharide (LPS)-resistant C3H/HeJ mice that have a defect in the Toll-like receptor 4 (TLR4) gene, both in vivo and in vitro, similarly to LPS (T. Monodane, Y. Kawabata, S. Yang, S. Hase, and H. Takada, J. Med. Microbiol. 50:4-12, 2001). In this study, we found that purified TUA (p-TUA) induced tumor necrosis factor alpha (TNF-alpha ) in murine monocytic J774.1 cells but not in mutant LR-9 cells expressing membrane CD14 at a lower level than the parent J774.1 cells. The TNF-alpha -inducing activity of p-TUA in J774.1 cells was completely inhibited by anti-mouse CD14 monoclonal antibody (MAb). p-TUA also induced interleukin-8 (IL-8) in human monocytic THP-1 cells differentiated to macrophage-like cells expressing CD14. Anti-human CD14 MAb, anti-human TLR4 MAb, and synthetic lipid A precursor IVA, an LPS antagonist, almost completely inhibited the IL-8-inducing ability of p-TUA, as well as LPS, in the differentiated THP-1 cells. Reduced p-TUA did not exhibit any activities in J774.1 or THP-1 cells. These findings strongly suggested that M. luteus TUA activates murine and human monocytic cells in a CD14- and TLR4-dependent manner, similar to LPS.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Tohoku University School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan. Phone: 81-22-717-8305. Fax: 81-22-717-8309. E-mail: dent-ht{at}mail.cc.tohoku.ac.jp.

Infection and Immunity, April 2001, p. 2025-2030, Vol. 69, No. 4
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.4.2025-2030.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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