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免疫功能正常的小鼠经皮感染枝孢菌后诱导产生固有和轻度的 Th17 皮肤免疫应答。

Innate and mild Th17 cutaneous immune responses elicited by subcutaneous infection of immunocompetent mice with Cladosporium cladosporioides.

机构信息

Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China.

Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China.

出版信息

Microb Pathog. 2022 Feb;163:105384. doi: 10.1016/j.micpath.2021.105384. Epub 2021 Dec 30.

DOI:10.1016/j.micpath.2021.105384
PMID:34974124
Abstract

Cladosporium cladosporioides is a dematiaceous hyphomycete that is pathogenic in the superficial and deep tissues of both immunodeficient and immunocompetent humans and animals. Our aim was to evaluate the antifungal immune responses elicited by C. cladosporioides in immunocompetent mice. Hence, we subcutaneously injected suspensions of C. cladosporioides spores into immunocompetent mice to investigate the anti-fungal immune responses in the skin. We collected skin tissue samples for histopathological examination, immunofluorescence staining, and quantitative real-time polymerase chain reaction analysis. We observed subcutaneous abscesses in mice after subcutaneous injection of C. cladosporioides. A large number of inflammatory cells, including dendritic cells, macrophages, and neutrophils, infiltrated the focal abscess, with comparatively few infiltrating inflammatory cells in the epidermal and dermal layers of the skin. We detected the expression of CD54 in the abscesses and the skin. Gene expression of the pattern recognition receptors Dectin-1 and TLR-2 was higher in infected mice than in controls. Gene expression of the cytokines IL-6, IL-1β, and IL-17A also increased after infection, suggesting that the Th17 signaling pathway may be involved in the anti-fungal response. Although the pathogenicity of C. cladosporioides in healthy mice was weak after subcutaneous infection, resulting in few serious pathological phenomena, it appears that innate and Th17 immune responses play important roles in the cutaneous host response to C. cladosporioides. These findings lay a foundation for further study of the pathogenic mechanism and treatment of C. cladosporioides infection.

摘要

枝孢霉是一种暗色丝孢霉,在免疫功能低下和免疫功能正常的人和动物的深部和表浅组织中均具有致病性。我们的目的是评估枝孢霉在免疫功能正常的小鼠中引发的抗真菌免疫反应。因此,我们将枝孢霉孢子混悬液皮下注射到免疫功能正常的小鼠中,以研究皮肤中的抗真菌免疫反应。我们收集皮肤组织样本进行组织病理学检查、免疫荧光染色和实时定量聚合酶链反应分析。我们观察到皮下注射枝孢霉后小鼠出现皮下脓肿。大量炎症细胞,包括树突状细胞、巨噬细胞和中性粒细胞,浸润在局灶性脓肿中,而表皮和真皮层中浸润的炎症细胞相对较少。我们在脓肿和皮肤中检测到 CD54 的表达。感染小鼠中模式识别受体 Dectin-1 和 TLR-2 的基因表达高于对照组。感染后细胞因子 IL-6、IL-1β 和 IL-17A 的基因表达也增加,表明 Th17 信号通路可能参与了抗真菌反应。尽管枝孢霉在健康小鼠中的致病性在皮下感染后较弱,导致很少出现严重的病理现象,但先天和 Th17 免疫反应似乎在宿主对枝孢霉的皮肤反应中发挥重要作用。这些发现为进一步研究枝孢霉感染的致病机制和治疗奠定了基础。

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