Induction of mucosal immunity to mycobacterial heat shock protein (hsp) 65 by colonic inoculation of plasmid DNA encoding hsp65

Abstract

Mycobacterial heat shock protein (hsp) 65 has more than 50% sequence homology with human hsp60 and immune responses against mycobacterial hsp65 may cross-react with human hsp60 and could cause autoimmune diseases including inflammatory bowel diseases (IBD). Since the colonic mucosa is a main inflammatory site in IBD, mucosal immunity to hsp65 may be more important for the mucosal inflammation than systemic immunity to hsp65. We inoculated plasmid DNA (pDNA) encoding mycobacterial hsp65 (pACB-hsp 65) into the colon of Wistar rats and evaluated the mucosal humoral immune response and the effect of these immune responses on the colonic mucosa. Four weeks after pDNA inoculation, significantly elevated titers of hsp65-specific IgA antibody were seen in fecal extracts of rats immunized intra-colonic mucosa with pACB-hsp65 (40±9U/ml), whereas the fecal IgA antibody titers of rats inoculated intradermal with pACB-hsp65 did not arise (8±5U/ml). Colonic inoculation of pACB-hsp65 induced systemic and mucosal immune responses to hsp65. However, macroscopic and histological examinations of the colonic mucosa inoculated with pACB-hsp65 showed no evidence of mucosal damage. These results suggested that the mucosal immunity to hsp65 on the colonic mucosa may not play a crucial role in the induction of colonic mucosal inflammation as was seen in IBD.