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Infection and Immunity, January 2005, p. 174-180, Vol. 73, No. 1
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.1.174-180.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

A Mutant of Staphylococcal Enterotoxin C Devoid of Bacterial Superantigenic Activity Elicits a Th2 Immune Response for Protection against Staphylococcus aureus Infection

Dong-Liang Hu,1 Jing-Chun Cui,1,2 Katsuhiko Omoe,3 Hiroshi Sashinami,1 Yuichi Yokomizo,4 Kunihiro Shinagawa,3 and Akio Nakane1*

Department of Bacteriology, Hirosaki University School of Medicine, Hirosaki,1 Department of Veterinary Microbiology, Faculty of Agriculture, Iwate University, Morioka, Iwate,3 Department of Immunology, National Institute of Animal Health, Tsukuba, Japan,4 Department of Bio-Engineering, Dalian Nationalities University, Dalian, People's Republic of China2

Received 14 July 2004/ Returned for modification 13 August 2004/ Accepted 17 September 2004

Staphylococcal enterotoxin C (SEC), a bacterial superantigenic exotoxin, is commonly produced by invasive Staphylococcus aureus isolates, especially methicillin-resistant strains and isolates from animal diseases. We constructed and expressed a nontoxic mutant SEC (mSEC) and investigated whether immunization with mSEC, which is devoid of superantigenic activity, can protect against S. aureus infection. Mice were immunized with mSEC and challenged with viable S. aureus. The bacterial counts in the organs of mSEC-immunized mice were significantly lower and the survival rate was higher than the corresponding values for the control group. Immunization with mSEC strongly induced the production of T-helper 2 type antibodies, immunoglobulin G1, and immunoglobulin G2b. The production of interleukin-10 (IL-10) and IL-4 was significantly greater in immunized mice challenged with S. aureus than in the control mice, whereas the production of gamma interferon (IFN-{gamma}) was significantly decreased in the immunized mice. The cytokine response in a spleen cell culture that was stimulated with heat-killed S. aureus or SEC showed that immunization with mSEC inhibited IFN-{gamma} production and up-regulated IL-10 production in vitro. Furthermore, IFN-{gamma} and tumor necrosis factor alpha production in vitro was significantly inhibited by sera from mSEC-immunized mice but not by sera from control mice. These results suggest that immunization with mSEC devoid of superantigenic properties provides protection against S. aureus infection and that the protection might be mediated by SEC-specific neutralizing antibodies.

* Corresponding author. Mailing address: Department of Bacteriology, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan. Phone: 81-172-39-5032. Fax: 81-172-39-5034. E-mail: a27k03n0{at}cc.hirosaki-u.ac.jp.

Editor: J. T. Barbieri

Infection and Immunity, January 2005, p. 174-180, Vol. 73, No. 1
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.1.174-180.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





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