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Alteration of murine immune response by Pseudomonas aeruginosa exotoxin A
Abstract:
Pseudomonas exotoxin A has been implicated as a possible virulence factor in Pseudomonas infections. This toxin has a direct cytotoxic effect on a number of cell types, including macrophages and their precursors, and therefore may affect other cells of the immune system. NFR/N(H-2q) (+/nu or nu/nu) mice were immunized with either T-dependent or T-independent antigens along with various doses of exotoxin A. The immune response was then assayed by a modification of the Jerne plaque assay. Exotoxin A induced a dose-dependent suppression of the in vitro and in vivo immune responses to T-dependent and T-independent antigens in immunocompetent +/nu mice. However, in NFR/N nu/nu mice, suppression of the immune response to the T-independent antigen trinitrophenylated-Ficoll was not observed. Instead, a marked enhancement of the response was observed at doses of 100 and 10 ng of exotoxin A. Removal of T-cells with anti-Thy 1.2 antiserum plus complement before antigen and exotoxin A stimulation in +/nu mice results in abrogation of the suppression. These data suggest that Pseudomonas exotoxin A exerts an effect on both B- and T-lymphocyte populations to modulate the immune response and that this activity may be one facet of the pathogenic effects of this toxin.
Insights
Pseudomonas exotoxin A suppresses immune responses in mice. This toxin impacts both B- and T-lymphocytes, potentially contributing to Pseudomonas infection pathogenesis.
Area of Science:
- Immunology
- Microbial Pathogenesis
Background:
- Pseudomonas exotoxin A is a virulence factor in Pseudomonas infections.
- The toxin exhibits cytotoxic effects on immune cells like macrophages.
Purpose of the Study:
- To investigate the immunomodulatory effects of Pseudomonas exotoxin A.
- To determine the role of T-lymphocytes in exotoxin A-induced immune suppression.
Main Methods:
- Mice were immunized with antigens and varying doses of exotoxin A.
- Immune responses were measured using a modified Jerne plaque assay.
- T-cells were depleted using anti-Thy 1.2 antiserum and complement.
Main Results:
- Exotoxin A caused dose-dependent suppression of immune responses in immunocompetent mice.
- In athymic mice, exotoxin A enhanced responses to T-independent antigens.
- T-cell depletion abrogated exotoxin A-induced suppression.
Conclusions:
- Pseudomonas exotoxin A modulates immune responses by affecting both B- and T-lymphocytes.
- These immunomodulatory activities may contribute to the pathogenic effects of the toxin.