# HOST DEFENSE MECHANISMS IN LEGIONELLA PNEUMONIA

> **NIH NIH R01** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 1988 · $204,032

## Abstract

Legionella pneumophila is an important cause of epidemic and sporadic human
pneumonia.  Intact recruited and immune inflammatory host defenses are
essential for successful containment of this infection in man and animals.
Critical interactions between cellular host defenses and Legionella can
only be inferred, but not proven from study of clinical material.  In vitro
studies with human calls are, of necessity, limited by the selection of an
artificial environment for culture.  We have developed a model of
Legionella pneumonia in rodents, which matches the human disease well.  We
have combined experiments performed in vitro and in vivo to supplement,
rather than to supplant the studies that are being performed in other
laboratories with human cells.  The primary infection can be divided into
phases:  1) initial unimpeded bacterial growth, 2) containment, and 3)
clearance and resolution.  A resident alveolar macrophage (AM) that is
permissive for bacterial growth characterizes susceptible species and is
probably necessary for productive infection.  Neutrophils (PMNL), in
contrast, provide the first protective defense against the bacteria.  When
examined in vitro phagocytes in the airspaces continue to support growth of
Legionella during the phase of resolution (a time when specific
immunological mechanisms have been activated), but they are less permissive
than resident cells.  We have demonstrated protection against rechallenge
in animals that have survived prior sublethal infection.  This protective
effect can be reproduced partially by passive transfer of antibody into
naive recipients.  We propose studies to increase our understanding of
immunological mechanisms in the successful containment of a primary
infection and in acquired resistance to re-infection.  We will characterize
the humoral and cellular immune response in the Lewis rat and in Strain 2
guinea pigs.  Subsequently, we will examine the effects of
immunosuppression and reconstitution in animals that demonstrate innate or
acquired resistance.  We will explore the role of the stimulated or
activated macrophage in the resistance to reinfection.  These studies will
increase our knowledge of immunity to an important human pathogen, but will
also add to our knowledge of host defenses against an important class of
human pathogens, pathogenic intracellular bacteria.

## Key facts

- **NIH application ID:** 3129980
- **Project number:** 5R01AI020365-06
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **SAM.gov UEI:** Z94KLERAG5V9
- **Principal Investigator:** WASHINGTON WINN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $204,032
- **Award type:** 5
- **Project period:** 1983-08-01 → 1990-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129980

## Citation

> US National Institutes of Health, RePORTER application 3129980, HOST DEFENSE MECHANISMS IN LEGIONELLA PNEUMONIA (5R01AI020365-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129980. Licensed CC0.

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