# IMMUNITY TO SALMONELLA INFECTION

> **NIH NIH R01** · TEMPLE UNIV OF THE COMMONWEALTH · 1992 · $167,169

## Abstract

We have discovered that an attenuated Salmonella vaccine induces superior
levels of protection in mice against challenge with virulent Salmonella,
tumoricidal and Leishmaniacidal macrophages, and paradoxically at the same
time induces profound immunosuppression of splenic mitogenic and in vitro
plaque-forming cell responses.  We have shown suppression is active, is
mediated by a non-H-@ restricted soluble factor, secreted by two
populations of cells:  adherent, phagocytic, esterase-positive macrophages,
and a second, newly defined population of nonadherent, nonphagocytic,
esterase-negative cells that contains 75% mononuclear cells with the
characteristics of macrophage precursors.  We have shown that suppression
is reversed by alphaIFNgamma, by IL-4, and by an inhibitor of reactive
nitrogen intermediates (RNI), N-monomethyl L-arginine.  Suppressor cells
produce RNI in culture, and the three inhibitors of suppression also
suppress nitrite accumulation.  Thus, nitric oxide or another RNI is
induced by the attenuated Salmonella and acts as a suppressor factor.  As
nitric oxide is also a known tumoricidal and microbicidal factor (for
eukaryotic pathogens) secreted by activated macrophages, the hypothesis is
formulated that Salmonella induce effector cells which mediate protection
and suppression through nitric oxide.  It is proposed to further
investigate these phenomena by 1) identifying more definitively the
suppressor and effector cells in the spleen and peritoneal cavity induced
by attenuated Salmonella, and seeing if they are the same or different; 2)
examining the cellular and cytokine pathway(s) required for induction of
suppression and suppressor cells, and testing if they are similar to or
different from the pathways leading to protection and to tumoricidal,
microbicidal and NK effector cells; 3) determining the target cell(s) of
the macrophage suppressor factor and the nature of the blockage in the
cellular and cytokine pathways which normally lead to immune responses; and
4) correlating the capacity of Salmonella vaccines to protect and to
suppress with production of reactive nitrogen intermediates (RNI) and
reactive oxygen intermediates (ROI).

The proposed studies on mechanisms of suppression induced by attenuated
Salmonella have application to development of vaccines, as suppression post
vaccination may be an unwanted side-effect of inoculation.  In a broader
context, the studies are of basic interest as they will further define the
properties of a population of cells in the monocyte/macrophage lineage
which are known to be suppressive, but which could also be effector cells.
These same cells may be induced by other inflammatory stimuli that result
in a mononuclear response.  Thus, these studies may elucidate fundamental
relationships between suppressive and potentiating effects of a variety of
infectious agents and biological response modifiers.

## Key facts

- **NIH application ID:** 3126280
- **Project number:** 2R01AI015613-12A1
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **SAM.gov UEI:** QD4MGHFDJKU1
- **Principal Investigator:** Toby K. Eisenstein
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $167,169
- **Award type:** 2
- **Project period:** 1978-12-01 → 1997-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126280

## Citation

> US National Institutes of Health, RePORTER application 3126280, IMMUNITY TO SALMONELLA INFECTION (2R01AI015613-12A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126280. Licensed CC0.

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