Remasking of Candida albicans β-Glucan in Response to Environmental pH Is Regulated by Quorum Sensing
Remasking of Candida albicans β-Glucan in Response to Environmental pH Is Regulated by Quorum Sensing
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DOI：
10.1128/mbio.02347-19
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发表时间：
2019-09-01
期刊：
影响因子：
6.4
通讯作者：
Hall, Rebecca A.
中科院分区：
文献类型：
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作者：
Cottier, Fabien;Sherrington, Sarah;Hall, Rebecca A.
白色念珠菌是人体肠道的一种寄生酵母，免疫系统可耐受，但有可能成为一种机会致病菌。C.白色念珠菌通过隐藏或暴露细胞壁病原体相关分子模式（PAMP）来实现这种双重性，以响应宿主来源的环境线索（pH、缺氧和乳酸）。这种细胞壁重塑使C.白念珠菌逃避或过度激活宿主的先天免疫反应，导致疾病。以前，我们表明，适应C。将白色念珠菌暴露于酸性环境（在雌性生殖道定殖期间遇到的条件）诱导显著的细胞壁重塑，导致两种关键真菌PAMP（β-葡聚糖和几丁质）暴露。在这里，我们报告说，这种pH依赖性细胞壁重塑是时间依赖性的，pH的初始变化驱动细胞壁暴露，然后在稍后的时间点重新掩蔽。β-葡聚糖的再掩蔽是通过细胞密度依赖性真菌群体感应分子法呢醇介导的，而几丁质的再掩蔽是通过小的、热稳定的、非蛋白质分泌分子介导的。转录谱分析确定了一组核心的42个基因显着调节pH值随时间的推移，并确定了转录因子Efg 1作为一个调节器的几丁质暴露通过调节CHT 2。这种动态的细胞壁重塑影响了C. albicans，提示在感染过程中，C.重要提示白色念珠菌是人类皮肤、胃肠道和生殖道微生物群的一部分，与我们共同进化了数千年。在此期间，C。白念珠菌已经开发出通过调节真菌细胞表面上关键表位的暴露来调节宿主的先天免疫应答的策略。在这里，我们报告说，暴露C。白色念珠菌进入酸性环境，类似于胃或阴道的酸性环境，增加了巨噬细胞对酵母的检测。然而，这种效应是暂时的，如C。白色念珠菌能够重新掩蔽这些表位（葡聚糖和几丁质）。我们发现葡聚糖的再掩蔽是由法尼醇的产生控制的，法尼醇是由C.白色念珠菌对高细胞密度的反应。然而，几丁质再掩蔽机制仍有待确定。通过了解环境感知和调节宿主-病原体相互作用之间的关系，开发创新的抗真菌策略的新机会是可能的。
Candida albicans is a commensal yeast of the human gut which is tolerated by the immune system but has the potential to become an opportunistic pathogen. One way in which C. albicans achieves this duality is through concealing or exposing cell wall pathogen-associated molecular patterns (PAMPs) in response to host-derived environment cues (pH, hypoxia, and lactate). This cell wall remodeling allows C. albicans to evade or hyperactivate the host's innate immune responses, leading to disease. Previously, we showed that adaptation of C. albicans to acidic environments, conditions encountered during colonization of the female reproductive tract, induces significant cell wall remodeling resulting in the exposure of two key fungal PAMPs (beta-glucan and chitin). Here, we report that this pH-dependent cell wall remodeling is time dependent, with the initial change in pH driving cell wall unmasking, which is then remasked at later time points. Remasking of beta-glucan was mediated via the cell density-dependent fungal quorum sensing molecule farnesol, while chitin remasking was mediated via a small, heat-stable, nonproteinaceous secreted molecule(s). Transcript profiling identified a core set of 42 genes significantly regulated by pH over time and identified the transcription factor Efg1 as a regulator of chitin exposure through regulation of CHT2. This dynamic cell wall remodeling influenced innate immune recognition of C. albicans, suggesting that during infection, C. albicans can manipulate the host innate immune responses.IMPORTANCE Candida albicans is part of the microbiota of the skin and gastrointestinal and reproductive tracts of humans and has coevolved with us for millennia. During that period, C. albicans has developed strategies to modulate the host's innate immune responses, by regulating the exposure of key epitopes on the fungal cell surface. Here, we report that exposing C. albicans to an acidic environment, similar to the one of the stomach or vagina, increases the detection of the yeast by macrophages. However, this effect is transitory, as C. albicans is able to remask these epitopes (glucan and chitin). We found that glucan remasking is controlled by the production of farnesol, a molecule secreted by C. albicans in response to high cell densities. However, chitin-remasking mechanisms remain to be identified. By understanding the relationship between environmental sensing and modulation of the host-pathogen interaction, new opportunities for the development of innovative antifungal strategies are possible.