Chitin-rich heteroglycan from Sporothrix schenckii sensu stricto potentiates fungal clearance in a mouse model of sporotrichosis and promotes macrophages phagocytosis

Lilin Huang,Weian Du,Huaiqiu Huang,Jing Zhang,Meirong Li,Rong Wu,Sanmei Chen,Xuchu Hu,Zixian Liang

doi:10.1186/s12866-021-02243-w

Abstract

BackgroundFungal cell wall polysaccharides maintain the integrity of fungi and interact with host immune cells. The immunomodulation of fungal polysaccharides has been demonstrated in previous studies. However, the effect of chitin-rich heteroglycan extracted from Sporothrix schenckiisensu stricto on the immune response has not been investigated.ResultsIn this study, chitin-rich heteroglycan was extracted from S. schenckiisensu stricto, and immunomodulation was investigated via histopathological analysis of skin lesions in a mouse model of sporotrichosis and evaluation of the phagocytic function and cytokine secretion of macrophages in vitro. The results showed that the skin lesions regressed and granulomatous inflammation was reduced in infected mice within 5 weeks. Moreover, heteroglycan promoted the fungal phagocytosis by macrophages and modulated the cytokine secretion. Heteroglycan upregulated TNF-α expression early at 24 h and IL-12 expression late at 72 h after incubation, which might result from moderate activation of macrophages and contribute to the subsequent adaptive immune response.ConclusionsChitin-rich heteroglycan extracted from S. schenckiisensu stricto potentiated fungal clearance in a mouse model of sporotrichosis. Moreover, chitin-rich heteroglycan promoted fungus phagocytosis by macrophages and modulated cytokines secretion. These results might indicate that chitin-rich heteroglycan could be considered as an immunomodulator used in the treatment of sporotrichosis.

Highlights

Sporotrichosis is a subcutaneous mycosis caused by traumatic inoculation of the dimorphic fungus Sporothrix schenckii complex, including S. schenckii s str, S. globosa, S. brasiliensis, and S. luriei [1]
The components and size of the heteroglycan extracted from S. schenckii s str We extracted heteroglycan from the mycelial form of S. schenckii s str and detected its components by highperformance liquid chromatography (HPLC)
According to the flow cytometry results, most heteroglycan microparticles were less than 10 μm, and half of them were less than 2 μm in size (Fig. 1D)

Summary

Introduction

Sporotrichosis is a subcutaneous mycosis caused by traumatic inoculation of the dimorphic fungus Sporothrix schenckii complex, including S. schenckii s str, S. globosa, S. brasiliensis, and S. luriei [1]. There are many polysaccharides on the cell wall of S. schenckii complex, and their distribution results in different virulence levels in the Galleria mellonella model [15]. This finding indicates that these polysaccharides might play important roles in modulating the immune response to the S. schenckii complex. We observed that chitin-rich heteroglycan exerted an antifungal response in a mouse model of sporotrichosis and modulated fungal phagocytosis and cytokines secretion by macrophages. The results here demonstrated that chitin-rich heteroglycan from S. schenckii s str might act as an immunomodulator in a mouse model of sporotrichosis. The effect of chitin-rich heteroglycan extracted from Sporothrix schenckii sensu stricto on the immune response has not been investigated

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