| Summary: | 碩士 === 國立臺灣大學 === 生命科學系 === 105 === Candida albicans is common commensal fungi in human. However, they can also cause fetal disease in immunocompromised patients. Neutrophils are the most abundant type of white blood cells in most mammals, and play a critical role in defense of fungal infection. Previous studies have shown that neutrophils trap and kill a variety of pathogens by neutrophil extracellular traps (NETs), whose formation depends on histone citrullination and dynamic microtubule networks. The guanine nucleotide exchange factor H1 (GEF-H1) is crucial in coupling microtubule dynamics to RhoA GTPase activation in a variety of normal biological situations. It is also a newly defined component of cellular defenses for the detection of microbial effectors during cell invasion by pathogens. However, it remains unknown whether GEF-H1 regulates NET formation in response to pathogen infection. Here I show that GEF-H1 did not affect granulopoiesis of neutrophils in the bone marrow. The actin and microtubule networks were comparable between mouse naïve wild-type and GEF-H1-deficient neutrophils. In naive state, the level of citrullinated histone 3 was reduced in GEF-H1–deficient neutrophils. After activation by phorbol 12-myristate 13-acetate (PMA), the rate of NET release was reduced in GEF-H1–deficient neutrophils compared to wild-type neutrophils. The reduced NET formation in GEF-H1-deificient neutrophils was not to due to the impaired reactive oxygen species (ROS) production. The decreased translocation of neutrophil elastase (NE) and myeloperoxidase (MPO) into nucleus and histone H3 citrulination was observed in GEF-H1-deficient neutrophils. I further found that GEF-H1 deficiency lead to impaired NET formation, ROS production and antifungal immunity in response to Candida albicans infection. Overall, our results suggested a potential role for GEF-H1 in the regulation of NET formation.
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