Species-Specific Immunological Reactivities Depend on the Cell-Wall Organization of the Two Aspergillus, Aspergillus fumigatus and A. flavus.

Sarah Sze Wah Wong,Audrey Beaussart,Jeya Maheshwari Jayapal,Jagadeesh Bayry,Lalitha Prajna,Dharmalingam Kuppamuthu,Lakshmi Prabha Venugopalan,Vishukumar Aimanianda,Stéphane Bretagne,Anupama Karnam,Mohammed Razeeth Shait Mohammed,Jean-Paul Latgé

doi:10.3389/fcimb.2021.643312

Abstract

Although belong to the same genus, Aspergillus fumigatus is primarily involved in invasive pulmonary infection, whereas Aspergillus flavus is a common cause of superficial infection. In this study, we compared conidia (the infective propagules) of these two Aspergillus species. In immunocompetent mice, intranasal inoculation with conidia of A. flavus resulted in significantly higher inflammatory responses in the lungs compared to mice inoculated with A. fumigatus conidia. In vitro assays revealed that the dormant conidia of A. flavus, unlike A. fumigatus dormant conidia, are immunostimulatory. The conidial surface of A. fumigatus was covered by a rodlet-layer, while that of A. flavus were presented with exposed polysaccharides. A. flavus harbored significantly higher number of proteins in its conidial cell wall compared to A. fumigatus conidia. Notably, β-1,3-glucan in the A. flavus conidial cell-wall showed significantly higher percentage of branching compared to that of A. fumigatus. The polysaccharides ensemble of A. flavus conidial cell wall stimulated the secretion of proinflammatory cytokines, and conidial cell wall associated proteins specifically stimulated IL-8 secretion from the host immune cells. Furthermore, the two species exhibited different sensitivities to antifungal drugs targeting cell wall polysaccharides, proposing the efficacy of species-specific treatment strategies. Overall, the species-specific organization of the conidial cell wall could be important in establishing infection by the two Aspergillus species.

Highlights

Chronic, allergic, and invasive forms of fungal infections account for over 1.6-million deaths annually; Aspergillus species are among the leading cause for mortality (Denning and Bromley, 2015; Bongomin et al, 2017; Cole et al, 2017)
There was no difference in the IL-10 level in the lungs of the mice inoculated with either of the Aspergillus conidia
We demonstrate that A. fumigatus and A. flavus conidia with different sizes, cell surface architectures and cell wall compositions, interact differentially with the host immune system

Summary

Introduction

Chronic, allergic, and invasive forms of fungal infections account for over 1.6-million deaths annually; Aspergillus species are among the leading cause for mortality (Denning and Bromley, 2015; Bongomin et al, 2017; Cole et al, 2017). The genus Aspergillus consists of a few hundred species (Geiser, 2009); the most common pathogenic species are A. fumigatus, A. flavus, A. terreus, and A. niger (Oliveira et al, 2015). These species are saprophytes with ubiquitous distribution, and are responsible for a wide clinical spectrum (Tekaia and Latge, 2005; Amaike and Keller, 2011). A. flavus is the predominant species causing IPA in Africa, Asia and Middle East, which is attributed to its ability to survive in humid environment (Rudramurthy et al, 2019)

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