Insights on the Functional Role of Beta-Glucans in Fungal Immunity Using Receptor-Deficient Mouse Models.

Mark Joseph Maranan Desamero,Soo-Hyun Chung,Shigeru Kakuta

doi:10.3390/ijms22094778

Abstract

Understanding the host anti-fungal immunity induced by beta-glucan has been one of the most challenging conundrums in the field of biomedical research. During the last couple of decades, insights on the role of beta-glucan in fungal disease progression, susceptibility, and resistance have been greatly augmented through the utility of various beta-glucan cognate receptor-deficient mouse models. Analysis of dectin-1 knockout mice has clarified the downstream signaling pathways and adaptive effector responses triggered by beta-glucan in anti-fungal immunity. On the other hand, assessment of CR3-deficient mice has elucidated the compelling action of beta-glucans in neutrophil-mediated fungal clearance, and the investigation of EphA2-deficient mice has highlighted its novel involvement in host sensing and defense to oral mucosal fungal infection. Based on these accounts, this review focuses on the recent discoveries made by these gene-targeted mice in beta-glucan research with particular emphasis on the multifaceted aspects of fungal immunity.

Highlights

Throughout the past decades, studies that focus on the carbohydrate-rich chemical compounds that are elaborated by food components and organisms have become a mainstay of intense scientific pursuits
Beta-glucan are obtained from diverse sources such as plants, cereals, algae, bacteria, and fungal entities, producing highly divergent biological effects owing to disparity in physicochemical properties; namely, tertiary configuration, solubility, length of polymer, molecular weight, and degree of branching [13,14]
We summarized the prevailing knowledge and recent discoveries in beta-glucan research, wherein we highlighted the utility of selected gene modified mice generated by our colleagues and others, and the compelling role they played in uncovering the functional contribution of beta-glucan and its signaling cascade in fungal immunity and resistance

Summary

Introduction

Throughout the past decades, studies that focus on the carbohydrate-rich chemical compounds that are elaborated by food components and organisms have become a mainstay of intense scientific pursuits. Biosensing of beta-glucans and other pathogen associated molecular patterns (PAMPs) is primarily reserved to a constellation of germ line-encoded molecules called pathogen recognition receptors (PRRs), which include the archetypal toll-like receptors (TLRs), as well as the non-TLR receptors, namely the C-type lectin receptors (CLRs), RIG-like helicases, cytosolic DNA sensors, and NOD-like receptors (NLRs) [17,18]. In the advent of gene targeting technologies [21], many investigators have taken advantage of the utility of beta-glucan receptor-deficient mouse models. Analysis of these gene-targeted mice has addressed the limitations imposed by using unpurified beta-glucan-containing materials such as the presence of contaminating microbial endotoxins (LPS) and, more importantly, underpins the direct involvement of the beta-glucan signaling pathway in disease resistance, progression, and susceptibility. We summarized the prevailing knowledge and recent discoveries in beta-glucan research, wherein we highlighted the utility of selected gene modified mice generated by our colleagues and others, and the compelling role they played in uncovering the functional contribution of beta-glucan and its signaling cascade in fungal immunity and resistance

Dectin-1 and Signaling Cascade

CR3 KO Mice

EphA2 KO Mice

Closing Remarks