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Infection and Immunity, May 2005, p. 2744-2750, Vol. 73, No. 5
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.5.2744-2750.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Identification of an Immunomodulating Agent from Mycobacterium leprae

Yumi Maeda,1 Tetsu Mukai,1 John Spencer,2 and Masahiko Makino1*

Department of Microbiology, Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aobacho, Higashimurayama, Tokyo 189-0002, Japan,1 Department of Microbiology, Colorado State University, Fort Collins, Colorado 80523-16772

Received 22 October 2004/ Returned for modification 1 December 2004/ Accepted 7 January 2005

A search for an immunomodulating agent from mycobacteria was carried out using Mycobacterium leprae. The antigenicity of each fraction of the bacterial membrane, which contains the most antigenic components of M. leprae, was assessed by using sera from paucibacillary leprosy. N-terminal sequencing of the serum-reactive protein and functional assessment of the membrane fractions using monocyte-derived dendritic cells (DCs) identified major membrane protein II (MMP-II) as one of the efficient T-cell-activating candidates. Purified MMP-II stimulated DCs from healthy individuals to produce interleukin-12 p70 and up-regulated the surface expression of major histocompatibility complex class I and II, CD86, and CD83 molecules. Also, there was an increase in the percentage of CD83+ cells in the DC population. Furthermore, MMP-II-pulsed DCs expressed their derivatives on their surfaces. Using Toll-like receptor 2 (TLR-2)-dependent receptor constructs, we found that TLR-2 signaling was involved in DC maturation induced by MMP-II. Taken together, MMP-II can be recognized as an immunomodulating protein in terms of activation of antigen-presenting cells and innate immunity.

* Corresponding author. Mailing address: Department of Microbiology, Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aobacho, Higashimurayama, Tokyo 189-0002, Japan. Phone: 81-42-391-8059. Fax: 81-42-391-8212. E-mail: mmaki{at}nih.go.jp.

Editor: W. A. Petri, Jr.

Infection and Immunity, May 2005, p. 2744-2750, Vol. 73, No. 5
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.5.2744-2750.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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