INFECTION OF EPITHELIAL-CELLS BY PATHOGENIC NEISSERIAE REDUCES THE LEVELS OF MULTIPLE LYSOSOMAL CONSTITUENTS

Members of our group reported recently that neisseria infection of hum an epithelial cells results in accelerated degradation of the major ly sosomal integral membrane protein LAMP1 and that this is due to hydrol ysis of this glycoprotein at its immunoglobulin Al (IgA1)-like hinge b y the neisseria type 2 IgA1 protease (L. Lin et al., Mel. Microbiol. 2 4:1083-1094, 1997). We also reported that the IgA1 protease plays a ma jor role in the ability of the pathogenic neisseriae to survive within epithelial cells and hypothesized that this is due to alteration of l ysosomes as a result of protease-mediated LAMP1 degradation. In this s tudy, we tested the hypothesis that neisseria infection leads to multi ple changes in lysosomes. Here, we report that neisseria infection als o reduces the levels of three other lysosomal markers: LAMP2, lysosoma l acid phosphatase (LAP), and CD63. In contrast, neither the epidermal growth factor receptor level nor the P-tubulin level is affected. A d etailed examination of LAMP2 indicated that the reduced LAMP2 levels a re not the result of an altered biosynthetic rate or of cleavage by th e IgA1 protease. Nevertheless, the protease plays a role in reducing L AMP2 and LAP activity levels, as these are partially restored in cells infected,vith an iga mutant. We conclude that neisseria infection res ults in multiple changes to the lysosomes of infected epithelial cells and that these changes are likely an indirect result of IgA1 protease -mediated cleavage of LAMP1.