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.
Highlights
Fungal diseases are a tremendous medical problem
This review describes our current understanding of the granules in immune cells
For CD8+ T cells, this process is mediated by engagement of the T-cell receptor (TCR)/CD3 complex, which lead to a signaling cascade utilizing Src family kinases, such as LymphoCyte-specific protein tyrosine Kinase (LCK), which phosphorylate immunoreceptor tyrosine-based activation motifs (ITAMs) Zeta-chain-Associated Protein kinase 70(ZAP70) Linker for Activation of T cells (LAT)/phospholipase Cγ (PLCγ)/interleukin-2-inducible T-cell kinase (ITK) Phosphatidylinositol 4,5-bisphosphate (PIP2) Inositol triphosphate (IP3) Ca2+ influx degranulation [37]
Summary
Fungal diseases are a tremendous medical problem. The frequency of fungal infections continues to climb, predominantly because of an increased number of immunocompromised and critically ill patients [1,2]. The therapeutic options for fungal infections are limited and associated with toxicities, which has led to an interest in immune therapeutic approaches [5] One such therapeutic target is granule-dependent release of antifungal molecules used in host defence. We highlight the similarities in different characteristics and processes in granule development, content, storage, signaling, trafficking, release, and function in various immune cell types during host defence against fungal infections. Understanding these characteristics may allow for knowledge transfer between scientists working with different cells and may lead to insights into the development of immunebased therapeutics for different cells employing similar granule-mediated mechanisms
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