Candida albicans bloodstream infection causes fungal septicaemia and death in over half of afflicted patients. Polymorphonuclear leukocytes (PMN) mediate defense against invasive candidiasis, but their role in protection versus tissue injury and sepsis is unclear. We observe PMN intravascular swarming and subsequent clustering in response to C. albicans yeast in a lethal septic mouse and human pulmonary circulation model. Live C. albicans sequester to the endothelium and are immediately captured by complement-dependent PMN chemotaxis, which is required for host survival. However, complement activation also leads to Leukotriene B4 (LTB4)-mediated intravascular PMN clustering and occlusion, resulting in capillaritis with pulmonary hemorrhage and hypoxemia. This clustering is unique to fungi and triggered by fungal cell wall components. PMN clustering is absent in mice lacking LTB4-receptor, and capillaritis is attenuated upon pharmacological LTB4 blockade without affecting phagocytosis. Therefore, therapeutically disrupting infection-induced capillaritis may limit organ injury without impairing host defense during fungal sepsis.

白色念珠菌的血液感染在一半以上的患者中引起真菌败血病和死亡。多形核白细胞（PMN）介导对侵袭性念珠菌病的防御，但它们在针对组织损伤和败血症的保护作用中的作用尚不清楚。我们观察到在致死性脓毒症小鼠和人类肺循环模型中，PMN血管内群群和随后的簇对白色念珠菌酵母的反应。活的白色念珠菌螯合内皮，并立即被补体依赖性PMN趋化性捕获，这是宿主生存所必需的。然而，补体激活也导致白三烯B4（LTB4）介导的血管内PMN聚集和闭塞，导致毛细血管炎伴肺出血和低氧血症。这种聚集是真菌特有的，并由真菌细胞壁成分触发。在缺乏LTB4受体的小鼠中不存在PMN聚集，并且在药理性LTB4阻滞作用下，毛细血管炎会减轻，而不会影响吞噬作用。因此，治疗性感染性毛细血管炎的破坏可以限制器官损伤，而不会损害真菌性败血症中的宿主防御能力。