Department of Immunobiology, University of Arizona, Tucson, Arizona, USA.
Department of Biology, Brooklyn College, Brooklyn, New York, USA.
mBio. 2019 Mar 12;10(2):e00218-19. doi: 10.1128/mBio.00218-19.
In patients with invasive fungal diseases, there is often little cellular inflammatory response. We tested the idea that binding of the human constitutive plasma protein serum amyloid P component (SAP) (also called PTX2) to dampens the innate immune response to this fungus. Many pathogenic fungi have cell surface amyloid-like structures important for adhesion and biofilm formation. Human SAP bound to fungi that expressed functional cell surface amyloid, but SAP had minimal binding to fungi with reduced expression of cell surface amyloid. In the absence of SAP, phagocytosis of fungi by human macrophages was potentiated by expression of amyloid on the fungi. SAP binding to fungi inhibited their phagocytosis by macrophages. Macrophages pretreated with SAP displayed reduced fungal phagocytosis, reduced secretion of inflammatory cytokines (IFN-γ, IL-6, and TNF-α), and increased secretion of the anti-inflammatory cytokine IL-10. SAP bound to fungi or added to the medium upregulated the expression of the anti-inflammatory receptor CD206 on macrophages. These findings suggest that SAP bound to amyloid-like structures on fungal cells dampens the host cellular immune response in fungal diseases such as invasive candidiasis. Macrophages are a key part of our innate immune system and are responsible for recognizing invading microbes, ingesting them, and sending appropriate signals to other immune cells. We have found that human macrophages can recognize invading yeast pathogens that have a specific molecular pattern of proteins on their surfaces: these proteins have structures similar to the structures of amyloid aggregates in neurodegenerative diseases like Alzheimer's disease. However, this surface pattern also causes the fungi to bind a serum protein called serum amyloid P component (SAP). In turn, the SAP-coated yeasts are poorly recognized and seldom ingested by the macrophages, and the macrophages have a more tolerant and less inflammatory response in the presence of SAP. Therefore, we find that surface structures on the yeast can alter how the macrophages react to invading microbes.
在患有侵袭性真菌病的患者中，通常很少有细胞炎症反应。我们检验了这样一种观点，即结合人固有血浆蛋白血清淀粉样蛋白 P 成分（SAP）（也称为 PTX2）可以减轻对这种真菌的固有免疫反应。许多致病性真菌具有对粘附和生物膜形成很重要的细胞表面淀粉样结构。人 SAP 结合到表达功能性细胞表面淀粉样结构的真菌上，但 SAP 与细胞表面淀粉样结构表达减少的真菌结合能力较弱。在没有 SAP 的情况下，真菌表面表达的淀粉样蛋白增强了人类巨噬细胞对真菌的吞噬作用。SAP 与真菌结合抑制了巨噬细胞对真菌的吞噬作用。用 SAP 预处理的巨噬细胞显示出真菌吞噬作用减少，炎症细胞因子（IFN-γ、IL-6 和 TNF-α）分泌减少，抗炎细胞因子 IL-10 分泌增加。SAP 与真菌结合或添加到培养基中会上调巨噬细胞上抗炎受体 CD206 的表达。这些发现表明，SAP 与真菌细胞上的淀粉样结构结合，可减轻侵袭性念珠菌病等真菌感染性疾病中宿主细胞免疫反应。巨噬细胞是我们固有免疫系统的关键部分，负责识别入侵的微生物，吞噬它们，并向其他免疫细胞发出适当的信号。我们发现，人类巨噬细胞可以识别表面具有特定蛋白质分子模式的入侵酵母病原体：这些蛋白质具有与阿尔茨海默病等神经退行性疾病中淀粉样蛋白聚集物相似的结构。然而，这种表面模式也导致真菌结合一种称为血清淀粉样蛋白 P 成分（SAP）的血清蛋白。反过来，SAP 包被的酵母很少被巨噬细胞识别和吞噬，并且在 SAP 存在的情况下，巨噬细胞具有更耐受和炎症反应更小的反应。因此，我们发现酵母表面结构可以改变巨噬细胞对入侵微生物的反应。
