Immune Cell Degranulation in Fungal Host Defence

Abstract

Humans have developed complex immune systems that defend against invading microbes, including fungal pathogens. Many highly specialized cells of the immune system share the ability to store antimicrobial compounds in membrane bound organelles that can be immediately deployed to eradicate or inhibit growth of invading pathogens. These membrane-bound organelles consist of secretory vesicles or granules, which move to the surface of the cell, where they fuse with the plasma membrane to release their contents in the process of degranulation. Lymphocytes, macrophages, neutrophils, mast cells, eosinophils, and basophils all degranulate in fungal host defence. While anti-microbial secretory vesicles are shared among different immune cell types, information about each cell type has emerged independently leading to an uncoordinated and confusing classification of granules and incomplete description of the mechanism by which they are deployed. While there are important differences, there are many similarities in granule morphology, granule content, stimulus for degranulation, granule trafficking, and release of granules against fungal pathogens. In this review, we describe the similarities and differences in an attempt to translate knowledge from one immune cell to another that may facilitate further studies in the context of fungal host defence.

Keywords: degranulation; granule; host defence; trafficking.

Figure 1

Panel A: Electron micrographs showing the heterogeneity of RNK-16 (NK cell) granules. (Aa) Type I granules. (Ab) A type II granule. (Ac) An intermediate granule with small cores (figure from [7] with permission). Panel B: rat mast cells with dark electron-dense granules (figure from [11] with permission). Panel C: cytoplasmic granules of eosinophils include many membrane-bound, large, dense, spherical, crystalloid-containing granules; less numerous, large, dense, spherical, crystalloid-free granules (figure from [12] with permission). PanelD: neutrophil morphology visualized by electron microscopy. (Top left, top right) The cytosol of a resting cell is filled with vesicles, with primary granules (P) staining intensely dark with diaminobenzidine, while secondary (S) and tertiary (T) granules show more translucent staining. Secretory vesicles (SV) are near the Golgi complex (G). Few mitochondria (M) are observed. (Bottom left, bottom right) (figure from [13] under Creative Commons Attribution License (CC BY)).

Figure 2

Canonical signaling pathways of granule trafficking.

Figure 3

Graphical representation of Stages of granule trafficking during an NK cell mediated cytotoxic event against fungal pathogen C. neoformans.