# IMMUNOMODIFIER ACTIVITIES OF PSEUDOMONAS EXOTOXIN A

> **NIH NIH R01** · UNIVERSITY OF MISSOURI-COLUMBIA · 1990 · $100,907

## Abstract

Microorganisms which succeed in overcoming the numerous and complex
mechanisms of the host immune system are able to invade and grow in the
host, thereby causing disease.  To escape the host's antimicrobial
immunity, the microorganism must evolve mechanisms which are capable of
interfering either with the host's innate immune system, the regulatory
system of the immune response or with its effector mechanisms.  In normal
animals immunocompetency is determined by delicate balance of positive and
negative signals.  If a microorganism disrupts this delicate balance,
harmful consequences may occur.  When the host is immunocompetent, an
invading microorganism may increase the existing imbalance of these
signals.  Such may be the case with the organism Pseudomonas aeruginosa.
P. aeruginosa has a predilection for immunocompromised individuals, those
patients which have an imbalance in their normal immune regulatory system.
The production of extracellular enzymes and/or toxins by P. aeruginosa
appears to play a significant role in the ability of this organism to cause
disease.  The most toxic substance produced by P. aeruginosa is exotoxin A
and thus it may play a significant role in the pathogenicity of the
organism.  We have previously shown that exotoxin A modulates the murine
immune response to a second antigen.  Depending on the immunocompetence of
the host, exotoxin A may exert its effect through different immune cell
populations.  This proposal intends to further extend these studies by
examining the specific mechanisms by which exotoxin A acts as a biological
response modifier.  In immunocompetent euthymic (+/nu) mice, we have shown
that exotoxin A can suppress the immune response to either thymus dependent
or thymus independent antigens by activating a suppressor T cell.
Characterization of the suppressor T cell and its suppressor factor(s) will
be forthcoming in this proposal.  In addition, we have also observed that
although exotoxin A does not induce suppression of the immune response to
the thymus independent antigen, TNP-Ficoll, in the immunoincompetent
athymic nu/nu mice, exotoxin A at higher doses is capable of inducing
enhanced immune responses to both thymus independent and thymus dependent
antigens in nude mice.  This enhanced response was found to be antigen
specific and not due to polyclonal B cell activation.  We have also
observed that exotoxin A is capable of inducing specific cell populations
to proliferate both in athymic (nu/nu) mice and in euthymic (+/nu) mice.
Experiments to delineate the mechanisms by which exotoxin A induces
proliferation of specific cells and enhances nude mice immune
responsiveness are outlined in this proposal.  These studies should
increase our understanding of the mechanisms by which bacterial derived
immunomodifiers (i.e., exotoxin A) function as immunomodulatory agents.

## Key facts

- **NIH application ID:** 3128750
- **Project number:** 5R01AI019359-08
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **SAM.gov UEI:** SZPJL5ZRCLF4
- **Principal Investigator:** MICHAEL Lee MISFELDT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $100,907
- **Award type:** 5
- **Project period:** 1983-08-01 → 1991-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3128750

## Citation

> US National Institutes of Health, RePORTER application 3128750, IMMUNOMODIFIER ACTIVITIES OF PSEUDOMONAS EXOTOXIN A (5R01AI019359-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3128750. Licensed CC0.

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