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Updated: Aug 18, 2026
Visualizing Non-lytic Exocytosis of Cryptococcus neoformans from Macrophages Using Digital Light Microscopy
Published on: October 21, 2014
Dynamic changes in the morphology of Cryptococcus neoformans during murine pulmonary infection
Marta Feldmesser1, Yvonne Kress1, Arturo Casadevall1
1Departments of Medicine, Division of Infectious Diseases1, Pathology2 and Microbiology and Immunology3, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Abstract:
The pathogenesis of Cryptococcus neoformans infection has been studied extensively with respect to inflammatory and pathological changes, but very little information is available regarding the morphology of yeast cells during the course of infection. Electron microscopy of Cryptococcus neoformans in murine pulmonary infection revealed increased cell wall thickness with time, but this difference was only partially accounted for by increases in cell diameter. Cell walls of melanized cells were thicker than those of nonmelanized cells 2 h after infection, and the cell wall of yeast became blacker with time, suggesting that melanization contributes to the increased cell wall thickness. Heterogeneous cell populations emerged, with the appearance of giant forms. While for C. neoformans ATCC strain 24067 (serotype D) the full spectrum of cell sizes were observed, for strains H99 (serotype A) and 3501 (serotype D) cells were divisible into two populations, giant and micro forms. In contrast to cellular heterogeneity, the epitope recognized by a protective mAb on the capsular glucuronoxylomannan (GXM) was found at all times of infection. Immunoelectron microscopy using mAbs to GXM demonstrated reactivity with intracellular structures, suggesting that synthesis of capsular polysaccharide occurs, at least in part, in the cytoplasm. In summary, the results indicate that: (i) the infection is dynamic with respect to yeast cell morphology; (ii) giant cell forms arise in tissue during the course of infection; (iii) cell walls blacken and thicken during the course of infection, consistent with melanin synthesis during infection; and (iv) GXM epitopes are found in the capsule, cell wall and cytoplasm, consistent with intracellular polysaccharide synthesis. The results indicate that the population of C. neoformans cells in tissue is in a highly dynamic state, implying that the immune system must confront cells with varying characteristics during the course of infection.
Insights
Cryptococcus neoformans infection dynamically alters yeast cell morphology, showing thickened, melanized cell walls and emerging giant forms. Capsular glucuronoxylomannan (GXM) synthesis appears to occur intracellularly during infection.
Area of Science:
- Mycology
- Infectious Diseases
- Cell Biology
Background:
- Pathogenesis of Cryptococcus neoformans infection is well-studied regarding inflammation and pathology.
- Limited information exists on yeast cell morphology during infection.
Purpose of the Study:
- To investigate the morphological changes of Cryptococcus neoformans yeast cells during murine pulmonary infection.
- To understand the dynamic nature of yeast cell populations in vivo.
Main Methods:
- Electron microscopy was used to examine yeast cells in murine pulmonary infection models.
- Immunoelectron microscopy with monoclonal antibodies (mAbs) against glucuronoxylomannan (GXM) was employed.
Main Results:
- Yeast cell walls increased in thickness and darkened over time, suggesting melanization.
- Heterogeneous cell populations emerged, including giant forms, with some strains showing distinct micro and giant populations.
- Glucuronoxylomannan (GXM) epitopes were detected in the cytoplasm, cell wall, and capsule, indicating intracellular synthesis.
Conclusions:
- Cryptococcus neoformans infection involves dynamic changes in yeast cell morphology, including cell wall thickening and melanization.
- Giant cell forms develop within host tissues during infection.
- Intracellular synthesis of capsular polysaccharide (GXM) occurs, contributing to the dynamic nature of the pathogen within the host.
