PDF(Pubmed)
Abstract：
The immunogenicity of Candida albicans cells is influenced by changes in the exposure of microbe-associated molecular patterns (MAMPs) on the fungal cell surface. Previously, the degree of exposure on the C. albicans cell surface of the immunoinflammatory MAMP β-(1,3)-glucan was shown to correlate inversely with colonisation levels in the gastrointestinal (GI) tract. This is important because life-threatening systemic candidiasis in critically ill patients often arises from translocation of C. albicans strains present in the patient\'s GI tract. Therefore, using a murine model, we have examined the impact of gut-related factors upon β-glucan exposure and colonisation levels in the GI tract. The degree of β-glucan exposure was examined by imaging flow cytometry of C. albicans cells taken directly from GI compartments, and compared with colonisation levels. Fungal β-glucan exposure was lower in the cecum than the small intestine, and fungal burdens were correspondingly higher in the cecum. This inverse correlation did not hold for the large intestine. The gut fermentation acid, lactate, triggers β-glucan masking in vitro, leading to attenuated anti-Candida immune responses. Additional fermentation acids are present in the GI tract, including acetate, propionate, and butyrate. We show that these acids also influence β-glucan exposure on C. albicans cells in vitro and, like lactate, they influence β-glucan exposure via Gpr1/Gpa2-mediated signalling. Significantly, C. albicans gpr1Δ gpa2Δ cells displayed elevated β-glucan exposure in the large intestine and a corresponding decrease in fungal burden, consistent with the idea that Gpr1/Gpa2-mediated β-glucan masking influences colonisation of this GI compartment. Finally, extracts from the murine gut and culture supernatants from the mannan grazing gut anaerobe Bacteroides thetaiotaomicron promote β-glucan exposure at the C. albicans cell surface. Therefore, the local microbiota influences β-glucan exposure levels directly (via mannan grazing) and indirectly (via fermentation acids), whilst β-glucan masking appears to promote C. albicans colonisation of the murine large intestine.
摘要：
白色念珠菌细胞的免疫原性受真菌细胞表面微生物相关分子模式（MAMPs）暴露变化的影响。以前,显示免疫炎性MAMPβ-（1,3）-葡聚糖在白色念珠菌细胞表面上的暴露程度与胃肠道（GI）中的定植水平成反比。这一点很重要，因为危重患者中危及生命的全身性念珠菌病通常是由患者胃肠道中存在的白色念珠菌菌株的易位引起的。因此,使用鼠类模型，我们研究了肠道相关因素对胃肠道β-葡聚糖暴露和定植水平的影响.通过直接从GI区室获取的白色念珠菌细胞的成像流式细胞术检查β-葡聚糖暴露程度，与殖民水平相比。盲肠中的真菌β-葡聚糖暴露低于小肠，盲肠中的真菌负担相应较高。这种逆相关性对于大肠不成立。肠道发酵酸，乳酸，在体外引发β-葡聚糖掩蔽，导致减弱的抗念珠菌免疫反应。额外的发酵酸存在于胃肠道中，包括醋酸盐,丙酸盐,还有丁酸盐.我们表明，这些酸也影响β-葡聚糖暴露在体外白色念珠菌细胞，像乳酸，它们通过Gpr1/Gpa2介导的信号传导影响β-葡聚糖暴露。重要的是,白色念珠菌gpr1Δgpa2Δ细胞在大肠中表现出升高的β-葡聚糖暴露和相应的真菌负荷降低,与Gpr1/Gpa2介导的β-葡聚糖掩蔽影响该GI区室定植的想法一致。最后,鼠肠的提取物和甘露聚糖放牧肠厌氧菌的培养上清液可促进白色念珠菌细胞表面的β-葡聚糖暴露。因此,局部微生物群直接（通过甘露聚糖放牧）和间接（通过发酵酸）影响β-葡聚糖暴露水平，而β-葡聚糖掩蔽似乎促进小鼠大肠的白色念珠菌定植。
