# MONONUCLEAR PHAGOCYTE KILLING OF LEISHMANIA PARASITES

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 1989 · $307,649

## Abstract

This project continues to have two long-term, interrelated objectives:
(a) to define the mechanisms by which Leishmania donovani (LD)
successfully parasitizes the tissue macrophage and thus causes persistent
visceral infection, and in parallel, (b) to determine what endogenous T
cell-dependent mechanisms (or exogenous immune products) are available to
the host to enable it to control and eradicate this intracellular
pathogen. These two objectives, whose ultimate intent is to improve the
treatment of patients with visceral leishmaniasis (VL), require focusing
not only the protozoan, its target cell (the macrophage). and the T cell,
but also on their interaction at multiple levels-in vitro, in the tissue,
and in the intact host. To extend our analysis of the key
immunopathogenic mechanisms in VL, our specific aims are to:  (1)
determine the mechanisms of production of leishmanial antigen-specific
interferon-gamma (IFN-gamma) and interleukin 2 (IL2); (2) characterize
the role of il2 in experimental VL; (3) determine the role of the
sensitized LYT-2+ cell in experimental VL; (4) examine the
antileishmanial and tissue effects of six selected cytokines: tumor
necrosis factor, interleukin 1, granulocyte-macrophage colony stimulating
factor, macrophage-colony stimulating factor, interleukin 3, and
interleukin 4; (5) extend our analysis of the LD- provoked tissue
granuloma to the influxing mononuclear phagocyte, in situ expression of
and requirement for soluble immune/inflammatory products, the effect of
suppressor mechanisms, and the basis of defective granuloma formation in
LD-infected C57BL/6-ep/ep mice; (6) characterize the immunologic
maintenance of resistance in experimental VL, and (7) determine if the
treatment of experimental VL can be enhanced by selected
immunotherapeutic agents (IFN-gamma, IL2, cytokines in Aim 4 which prove
effective) (a) using in alone. (b) synergistically with conventional
chemotherapy (Pentostam), or (c) combination with antisuppressor
treatments with or without Pentostam. We anticipate that the proposed
detailed analysis, to be conducted at the cellular, tissue, and intact
host levels, will provide a rationale basis for approaching the future
pharmacologic/immunologic management of world-wide infections caused by
L. donovani and other strains of Leishmania.

## Key facts

- **NIH application ID:** 3126939
- **Project number:** 2R01AI016963-10
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **SAM.gov UEI:** YNT8TCJH8FQ8
- **Principal Investigator:** HENRY W. MURRAY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $307,649
- **Award type:** 2
- **Project period:** 1980-09-30 → 1994-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126939

## Citation

> US National Institutes of Health, RePORTER application 3126939, MONONUCLEAR PHAGOCYTE KILLING OF LEISHMANIA PARASITES (2R01AI016963-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126939. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*