Journal
CELL HOST & MICROBE
Volume 23, Issue 1, Pages 121-+Publisher
CELL PRESS
DOI: 10.1016/j.chom.2017.11.009
Keywords
-
Categories
Funding
- Canadian Institutes of Health Research (CIHR) [RS-342013]
- Department of Critical Care Medicine from the University of Calgary Medical Group (UCMG)
- University of Calgary
- Canadian Foundation for Innovation's
- Beverley Phillips Rising Star Program
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available