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Infection and Immunity, February 2001, p. 810-815, Vol. 69, No. 2
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.2.810-815.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Trehalose 6,6'-Dimycolate (Cord Factor) of Mycobacterium tuberculosis Induces Foreign-Body- and Hypersensitivity-Type Granulomas in Mice

Hirokazu Yamagami,1,2,* Takayuki Matsumoto,2 Nagatoshi Fujiwara,1 Tetsuo Arakawa,2 Kenji Kaneda,3 Ikuya Yano,4 and Kazuo Kobayashi1

Departments of Host Defense,1 Gastroenterology,2 and Anatomy,3 Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, and Institute of BCG, Kiyose-shi, Tokyo 204-0022,4 Japan

Received 17 July 2000/Returned for modification 14 September 2000/Accepted 8 November 2000

Granulomatous inflammation is characterized morphologically by a compact organized collection of macrophages and their derivatives. It is classified as either a hypersensitivity type or a foreign-body type. Lipid components of the Mycobacterium tuberculosis cell wall participate in the pathogenesis of infection. Strains of M. tuberculosis have cord factor (trehalose 6,6'-dimycolate [TDM]) on their surface. To clarify host responses to TDM, including immunogenicity and pathogenicity, we have analyzed the footpad reaction, histopathology, and cytokine profiles of experimental granulomatous lesions in immunized and unimmunized mice challenged with TDM. In the present study, we have demonstrated for the first time that TDM can induce both foreign-body-type (nonimmune) and hypersensitivity-type (immune) granulomas by acting as a nonspecific irritant and T-cell-dependent antigen. Immunized mice challenged with TDM developed more severe lesions than unimmunized mice. At the active lesion, we found monocyte chemotactic, proinflammatory, and immunoregulatory cytokines. The level was enhanced in immunized mice challenged with TDM. This result implies that both nonimmune and immune mechanisms participate in granulomatous inflammation induced by mycobacterial infection. Taken together with a previous report, this study shows that TDM is a pleiotropic molecule against the host and plays an important role in the pathogenesis of tuberculosis.

* Corresponding author. Mailing address: Department of Host Defense, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. Phone: 81-6-6645-3746. Fax: 81-6-6645-3747. E-mail: yamagami{at}med.osaka-cu.ac.jp.

Infection and Immunity, February 2001, p. 810-815, Vol. 69, No. 2
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.2.810-815.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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