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

Author:

Shibata Yoshimi1,Honda Ikuro2,Justice J. Paul1,Van Scott Michael R.1,Nakamura Reiko M.2,Myrvik Quentin N.3

Affiliation:

1. Department of Physiology, East Carolina University Brody School of Medicine, Greenville, North Carolina 278581;

2. Japan BCG Laboratory, Tokyo, Japan2; and

3. Myrvik Enterprises, Southport, North Carolina 284613

Abstract

ABSTRACT 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-γ) production, which plays a Th1 adjuvant role. However, HK BCG further induces prostaglandin E 2 -releasing spleen macrophages (Mφ) (PGE 2 -Mφ), which potentially inhibit Th1 adjuvant activities. We found that chitin particles did not induce PGE 2 -Mφ 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-γ-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.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Immunology,Microbiology,Parasitology

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