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Infection and Immunity, October 2001, p. 6123-6130, Vol. 69, No. 10
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.10.6123-6130.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Th1 Adjuvant N-Acetyl-D-Glucosamine Polymer Up-Regulates Th1 Immunity but Down-Regulates Th2 Immunity against a Mycobacterial Protein (MPB-59) in Interleukin-10-Knockout and Wild-Type Mice

Yoshimi Shibata,1,* Ikuro Honda,2 J. Paul Justice,1 Michael R. Van Scott,1 Reiko M. Nakamura,2 and Quentin N. Myrvik3

Department of Physiology, East Carolina University Brody School of Medicine, Greenville, North Carolina 278581; Japan BCG Laboratory, Tokyo, Japan2; and Myrvik Enterprises, Southport, North Carolina 284613

Received 20 February 2001/Returned for modification 4 April 2001/Accepted 11 July 2001

Treatment of mice with heat-killed (HK) Mycobacterium bovis BCG or 1- to 10-µm chitin particles (nonantigenic N-acetyl-D-glucosamine polymers) is known to induce innate immune responses, including gamma interferon (IFN-gamma ) production, which plays a Th1 adjuvant role. However, HK BCG further induces prostaglandin E2-releasing spleen macrophages (Mphi ) (PGE2-Mphi ), which potentially inhibit Th1 adjuvant activities. We found that chitin particles did not induce PGE2-Mphi formation. To further assess whether chitin has Th1 adjuvant effects, interleukin-10 (IL-10)-knockout (KO) mice and their wild-type (WT, C57BL/6) controls were immunized with a 30-kDa MPB-59 mycobacterial protein mixed with chitin. Immunization with MPB-59 alone induced Th2 responses, characterized by increases in total serum immunoglobulin E (IgE) and specific serum IgG1 levels and spleen Th2 cells producing IL-4, IL-5, and IL-10. No IFN-gamma -producing spleen Th1 cells, specific serum IgG2a, or delayed-type hypersentivity (DTH) footpad reactions were detected. On the other hand, chitin-MPB-59 immunization significantly increased spleen Th1 responses, DTH reaction, and serum IgG2a levels along with decreases of Th2 responses. The magnitude of these Th1 adjuvant effects was greater in IL-10-KO mice than in WT mice. In contrast, immunization with HK BCG-MPB-59 showed little or no Th1 adjuvant effect. These data indicate that chitin has a unique Th1 adjuvant effect on the development of Th1 immunity against a mycobacterial antigen. IL-10 down-regulates the adjuvant effect of chitin.

* Corresponding author. Mailing address: Department of Physiology, East Carolina University Brody School of Medicine, Greenville, NC 27858. Phone: (252) 816-1905. Fax: (252) 816-3460. E-mail: shibatay{at}mail.ecu.edu.

Infection and Immunity, October 2001, p. 6123-6130, Vol. 69, No. 10
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.10.6123-6130.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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