Activation of HIF-1α and LL-37 by commensal bacteria inhibits Candida albicans colonization.
Activation of HIF-1α and LL-37 by commensal bacteria inhibits Candida albicans colonization.
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侵袭性疾病需要白色念珠菌定植。与人类不同，具有成熟完整肠道微生物群的成年小鼠对C。胃肠道（GI）白色念珠菌定植。但促进C.白色念珠菌定植抗性未知。在这里，我们证明了肠道厌氧菌-特别是厚壁梭菌（簇IV和XIVa）和拟杆菌-是维持C。小鼠对白色念珠菌定植的抵抗力。以多形拟杆菌为模型生物，我们发现HIF-1α（一种激活先天免疫效应的重要转录因子）和抗菌肽LL 37-CRAMP是C.白念珠菌定植抗性。抗生素治疗使C.白念珠菌定植，结肠Hif 1a的药理学激活诱导CRAMP表达并导致C.白色念珠菌胃肠道定植和50%的死亡率降低侵袭性疾病。在抗生素的背景下，B需要Hif 1a和Cramp。图4示出了泰奥塔米隆诱导的针对肠道CA定殖的保护。因此，C.通过激活肠粘膜免疫效应子调节白色念珠菌GI定植可能代表了预防人类侵袭性真菌病的新治疗方法。
Candida albicans colonization is required for invasive disease. Unlike humans, adult mice with mature intact gut microbiota are resistant to C. albicans gastrointestinal (GI) colonization. But the factors that promote C. albicans colonization resistance are unknown. Here we demonstrate that commensal anaerobic bacteria – specifically Clostridial Firmicutes (Clusters IV and XIVa) and Bacteroidetes – are critical for maintaining C. albicans colonization resistance in mice. Using Bacteroides thetaiotamicron as a model organism, we find that HIF-1α, a transcription factor important for activating innate immune effectors, and the antimicrobial peptide LL37-CRAMP are key determinants of C. albicans colonization resistance. While antibiotic treatment enables C. albicans colonization, pharmacologic activation of colonic Hif1a induces CRAMP expression and results in a significant reduction of C. albicans GI colonization and a 50% decrease in mortality from invasive disease. In the setting of antibiotics, Hif1a and Cramp are required for B. thetaiotamicron-induced protection against CA colonization of the gut. Thus, C. albicans GI colonization modulation by activation of gut mucosal immune effectors may represent a novel therapeutic approach for preventing invasive fungal disease in humans.