Division of Infectious Diseases, Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Division of Infectious Diseases, Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Cell Host Microbe. 2019 Mar 13;25(3):404-417.e6. doi: 10.1016/j.chom.2019.02.004.
Mucosal barriers are densely colonized by pathobiont microbes such as Candida albicans, capable of invasive disseminated infection. However, systemic infections occur infrequently in healthy individuals, suggesting that pathobiont commensalism may elicit host benefits. We show that intestinal colonization with C. albicans drives systemic expansion of fungal-specific Th17 CD4 T cells and IL-17 responsiveness by circulating neutrophils, which synergistically protect against C. albicans invasive infection. Protection conferred by commensal C. albicans requires persistent fungal colonization and extends to other extracellular invasive pathogens such as Staphylococcus aureus. However, commensal C. albicans does not protect against intracellular influenza virus infection and exacerbates allergic airway inflammation susceptibility, indicating that positively calibrating systemic Th17 responses is not uniformly beneficial. Thus, systemic Th17 inflammation driven by CD4 T cells responsive to tonic stimulation by commensal C. albicans improves host defense against extracellular pathogens, but with potentially harmful immunological consequences.
黏膜屏障被条件致病菌微生物（如白色念珠菌）密集定植，这些微生物能够引发侵袭性播散性感染。然而，健康个体中系统性感染很少发生，这表明条件致病菌共生可能会给宿主带来益处。我们发现，白色念珠菌在肠道中的定植会驱动系统性扩展真菌特异性 Th17 CD4 T 细胞和循环中性粒细胞对 IL-17 的反应性，它们协同保护宿主免受白色念珠菌侵袭性感染。由共生白色念珠菌赋予的保护作用需要持续的真菌定植，并扩展到其他细胞外侵袭性病原体，如金黄色葡萄球菌。然而，共生白色念珠菌并不能预防细胞内流感病毒感染，反而会加剧过敏气道炎症的易感性，表明系统性 Th17 反应的积极校准并不完全有益。因此，由对共生白色念珠菌的持续刺激作出反应的 CD4 T 细胞驱动的系统性 Th17 炎症会改善宿主对细胞外病原体的防御能力，但也可能带来潜在的有害免疫后果。
