Department of Pathology, University of Arizona, Tucson, AZ, USA.
J Infect Dis. 2012 Nov;206(9):1473-8. doi: 10.1093/infdis/jis464. Epub 2012 Jul 16.
Invasive candidiasis occurs in the gastrointestinal tract, especially in neutropenic patients. We were interested in determining whether invasive fungi formed amyloid in humans as they are known to do in vitro. We also sought to characterize the consequence(s) of such amyloid formation.
Tissue from 25 autopsy patients with invasive candidiasis of the gastrointestinal tract was stained with amyloidophilic dyes and for the presence of serum amyloid P component (SAP). Confirmation of the interaction of SAP and Candida was demonstrated using Candida albicans and mutants for amyloid formation.
Amyloid was present on the cellular surface of fungi invading gut tissue. Moreover, SAP bound to the fungal cell walls, confirming the presence of amyloid. In vitro observations showed SAP bound avidly to fungi when amyloid formed in fungal cell walls. An unexpected result was the lack of host neutrophils in response to the invading fungi, not only in neutropenic patients but also in patients with normal or increased white blood counts.
We report the first demonstration of functional fungal amyloid in human tissue and the binding of SAP to invading fungi. It is postulated that fungal amyloid, SAP, or a complex of the proteins may inhibit the neutrophil response.
侵袭性念珠菌病发生在胃肠道,特别是中性粒细胞减少的患者中。我们感兴趣的是确定侵袭性真菌是否像在体外那样形成淀粉样蛋白。我们还试图描述这种淀粉样蛋白形成的后果。
对 25 例胃肠道侵袭性念珠菌病尸检患者的组织进行淀粉样蛋白亲染料和血清淀粉样蛋白 P 成分 (SAP) 染色。使用白色念珠菌和淀粉样形成突变体证明 SAP 与念珠菌的相互作用。
在入侵肠道组织的真菌的细胞表面存在淀粉样蛋白。此外,SAP 与真菌细胞壁结合,证实了淀粉样蛋白的存在。体外观察表明,当真菌细胞壁中形成淀粉样蛋白时,SAP 与真菌紧密结合。一个意外的结果是,不仅在中性粒细胞减少的患者中,而且在白细胞计数正常或增加的患者中,都缺乏对入侵真菌的宿主中性粒细胞的反应。
我们首次报告了功能性真菌淀粉样蛋白在人体组织中的存在以及 SAP 与入侵真菌的结合。据推测,真菌淀粉样蛋白、SAP 或其复合物可能抑制中性粒细胞的反应。