# CRYPTOCOCCAL POLYSACCHARIDE:  INHIBITION OF PHAGOCYTOSIS

> **NIH NIH R01** · UNIVERSITY OF NEVADA RENO · 1988 · $157,063

## Abstract

The capsule is closely associated with the virulence of Cryptococcus
neoformans.  The capsule inhibits phagocytosis of the yeast by macrophages,
monocytes, and neutrophils.  More recent studies in our laboratory have
shown that incubation of encapsulated cryptococci with normal human serum
leads to deposition of large amounts of C3 and C3 fragments and lesser
amounts of IgG within the capsule and at the capsular surface.  Thus, the
capsule mediates two biological functions with opposing effects.  It is our
current view that phagocytosis of the yeast is dependent upon a balance
between the antiphagocytic action of cryptococcal polysaccharide and the
ability of the yeast to focus opsonically active complement fragments and
IgG at the capsular surface.

The proposed studies will 1) determine the function and antigenic
specificity of IgG that is deposited from normal human serum into the
capsule; 2) determine the mode of activation, mechanism of binding,
molecular form, and molecular activator of C3 that binds to the capsule; 3)
determine whether cryptococcal isolates differ in ability to localize
opsonic fragments of C3 and/or IgG at the capsular surface; 4) examine the
influence of phagocyte activation on phagocytosis of C. neoformans; and 5)
determine the influence of neutrophil oxidative metabolites on complement
activation by cryptococcal polysaccharide.

The significance of the proposed study lies in our ability to understand
the mechanism of action of a major virulence factor of a medically
important yeast.  Cryptococcosis is of increasing clinical importance in
patients whose immune systems are compromised by cancer chemotherapy or
AIDS.  The capsule is the interface between C. neoformans and the defense
mechanisms of the body.  An understanding of the molecular mechanisms of
this interaction is fundamental to understanding the pathobiology of the
disease and provides a framework for therapeutic modification of
host-parasite interaction.

## Key facts

- **NIH application ID:** 3125682
- **Project number:** 5R01AI014209-11
- **Recipient organization:** UNIVERSITY OF NEVADA RENO
- **SAM.gov UEI:** WLDGTNCFFJZ3
- **Principal Investigator:** Thomas R Kozel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $157,063
- **Award type:** 5
- **Project period:** 1977-07-01 → 1989-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3125682

## Citation

> US National Institutes of Health, RePORTER application 3125682, CRYPTOCOCCAL POLYSACCHARIDE:  INHIBITION OF PHAGOCYTOSIS (5R01AI014209-11). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3125682. Licensed CC0.

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