Role of sphingomyelin synthase in controlling the antimicrobial activity of neutrophils against Cryptococcus neoformans.

ABSTRACT: The key host cellular pathway(s) necessary to control the infection caused by inhalation of the environmental fungal pathogen Cryptococcus neoformans are still largely unknown. Here we have identified that the sphingolipid pathway in neutrophils is required for them to exert their killing activity on the fungus. In particular, using both pharmacological and genetic approaches, we show that inhibition of sphingomyelin synthase (SMS) activity profoundly impairs the killing ability of neutrophils by preventing the extracellular release of an antifungal factor(s). We next found that inhibition of protein kinase D (PKD), which controls vesicular sorting and secretion and is regulated by diacylglycerol (DAG) produced by SMS, totally blocks the extracellular killing activity of neutrophils agains

SUBMITTER: Qureshi A 

PROVIDER: S-EPMC3011003 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature