Epithelial application of Pseudomonas aeruginosa exotoxin A results in a selective targeting to cells in the liver, spleen and lymph node

Pseudomonas aeruginosa exotoxin A (PE) is a 67-kDa protein expressed under the selective pressure of a low iron environment. Previous studies using no n-toxic PE chimeras containing a viral surface antigen, the V3 loop of MN g p120 from human immunodefiency virus type 1 (HIV-1), resulted in not only a n effective mucosal immunization but also a striking systemic immune respon se following epithelial application, presently, we have examined the possib ility that such a strong dual immune response was generated by the efficien t targeting of critical cells of the immune system. Mice were dosed with 10 mu g of toxic PE or a non-toxic mutant of PE (ntPE) by intratracheal insti llation. Examination of lung, liver and spleen tissues isolated 1, 8 and 12 h following intratracheal instillation with PE demonstrated specific cell damage in these tissues which was not observed in mice dosed with ntPE. Bas ed upon the location and characteristics of observed responses, the cells t argeted by PE appear to be involved in the antigen presentation arm of the immune response. Since ntPE chimeras with inserted peptide antigen epitopes from a wide variety of pathogens are easy to prepare and administer, these results support this approach fur mucosal immunization. (C) 2000 Elsevier Science B.V. All rights reserved.