Mucosal IgA Prevents Commensal Candida albicans Dysbiosis in the Oral Cavity.

Mucosal IgA Prevents Commensal Candida albicans Dysbiosis in the Oral Cavity.
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DOI:
10.3389/fimmu.2020.555363
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发表时间:
2020
影响因子:
7.3
通讯作者:
Swidergall M
Swidergall M
中科院分区:
医学2区
文献类型:
--
作者:
Millet N;Solis NV;Swidergall M

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真菌白色念珠菌定殖口腔粘膜表面的健康个体的30-70%。由于局部或全身免疫抑制,这种共生真菌能够增殖,导致口腔疾病,称为口咽念珠菌病(OPC)。然而,在健康的个体中,白色念珠菌不会造成伤害。与人类不同,小鼠的真菌群中没有白色念珠菌。因此,口腔真菌攻击产生急性免疫反应在一个幼稚的宿主。因此,我们利用能够在口腔中持续存在而不引起疾病的白色念珠菌临床分离株来分析对口腔真菌共生的适应性反应。我们进行了RNA测序,以确定白色念珠菌定植期间的转录宿主反应景观。途径分析显示,由于白色念珠菌的口腔持久性,适应性宿主反应上调,包括免疫网络对IgA产生的上调。真菌定植增加了唾液和舌头的跨特异性IgA水平,IgA+细胞迁移到真菌定植的病灶。IgA的结合阻止了真菌上皮的粘附和侵袭,从而抑制了促炎上皮的反应。除了CD19+ CD138−B细胞外,在白色念珠菌定植的小鼠的舌头上还富集了质母细胞和浆细胞,这表明B淋巴细胞在口腔真菌定植过程中发挥了潜在的作用。B细胞缺乏增加了口腔真菌负荷,但没有引起严重的OPC。因此,在口腔中,B淋巴细胞通过在定植病灶分泌IgA来控制共生白色念珠菌的携带,从而防止真菌生态失调。
The fungus Candida albicans colonizes the oral mucosal surface of 30–70% of healthy individuals. Due to local or systemic immunosuppression, this commensal fungus is able to proliferate resulting in oral disease, called oropharyngeal candidiasis (OPC). However, in healthy individuals C. albicans causes no harm. Unlike humans mice do not host C. albicans in their mycobiome. Thus, oral fungal challenge generates an acute immune response in a naive host. Therefore, we utilized C. albicans clinical isolates which are able to persist in the oral cavity without causing disease to analyze adaptive responses to oral fungal commensalism. We performed RNA sequencing to determine the transcriptional host response landscape during C. albicans colonization. Pathway analysis revealed an upregulation of adaptive host responses due to C. albicans oral persistence, including the upregulation of the immune network for IgA production. Fungal colonization increased cross-specific IgA levels in the saliva and the tongue, and IgA+ cells migrated to foci of fungal colonization. Binding of IgA prevented fungal epithelial adhesion and invasion resulting in a dampened proinflammatory epithelial response. Besides CD19+ CD138− B cells, plasmablasts, and plasma cells were enriched in the tongue of mice colonized with C. albicans suggesting a potential role of B lymphocytes during oral fungal colonization. B cell deficiency increased the oral fungal load without causing severe OPC. Thus, in the oral cavity B lymphocytes contribute to control commensal C. albicans carriage by secreting IgA at foci of colonization thereby preventing fungal dysbiosis.
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