# NATURAL CELL-MEDIATED RESISTANCE IN CRYPTOCOCCOSIS

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 1989 · $154,735

## Abstract

Cells and mechanisms involved in natural cell mediated resistance against
the yeast-like organism, Cryptococcus neoformans are not well defined.
There are three different cell populations in normal unstimulated animals
which have the potential to clear cryptococci from tissues.  These are
polymorphonuclear leukocytes (PMNL), macrophages, and natural killer (NK)
cells.  Over the past three years, we have studied the effects of natural
effector cells on C. neoformans both in vivo and in vitro.  From these
studies, it is clear that normal mice have cells which have
anti-Cryptococcus activity and by numerous criteria, have characteristics
matching NK cells.  Although NK cells are not capable of sterilizing a
culture of 10/3 cryptococci nor totally eliminating C. neoformans from mice
infected with 10/4 organisms, they do significantly reduce the numbers of
cryptococci in both cases.  These findings suggest that NK cells
participate along with PMNL and macrophages in initial clearance of
cryptococci from host tisuses.  NK cells affect C. neoformans by a
nonphagocytic mechanism which includes first binding of the NK cells to the
organism then later inhibiting the growth of the cryptococci.  The lytic
effects of cytotoxic T lymphocytes (CTL) and NK cells against appropriate
tissue targets appear to be the result of effector cell exocytosis of
granules containing cytolytic components.  We are proposing that a similar
mechanism may be operating in NK cell mediated inhibition of cryptococci
growth.  However, our earlier studies have shown that the kinetics of NK
cell binding to cryptococci and inhibition of cryptococci growth are much
slower than with tumor cell targets.  This suggests there may be
differences in the way the NK cells respond to binding of cryptococci
targets versus tumor cell targets and in the active components or the means
by which active components of NK cells affect the yeast target.  We now
propose investigations to gain a basic understanding of interactions of NK
cells with cryptococci, a target which is substantially different from
previously studied NK targets.  To do this we will determine the sequence
of steps leading to inhibition of cryptococci growth, study the changes
occurring in the effector and target cells after binding using light and
electron microscopy techniques, and asses what specific component(s) of the
NK cells is responsible for the anti-Cryptococcus activity.  These studies
should provide new and significant information on the mechanisms of natural
cell mediated resistance in cryptococcosis.

## Key facts

- **NIH application ID:** 3128296
- **Project number:** 5R01AI018895-08
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **SAM.gov UEI:** GY8NMUZQXVS7
- **Principal Investigator:** JUNEANN W MURPHY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $154,735
- **Award type:** 5
- **Project period:** 1989-01-01 → 1991-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3128296

## Citation

> US National Institutes of Health, RePORTER application 3128296, NATURAL CELL-MEDIATED RESISTANCE IN CRYPTOCOCCOSIS (5R01AI018895-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3128296. Licensed CC0.

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