2017年伍安怡老師實驗室論文發表
 

 2017年伍安怡老師實驗室論文發表--博士後研究員巫聖揚

Cell Intrinsic Galectin-3 Attenuates Neutrophil ROS-Dependent Killing of Candida by Modulating CR3 Downstream Syk Activation

Sheng-Yang Wu1, Juin-Hua Huang1, Wen-Yu Chen1, Yi-Chen Chan2, Chun-Hung Lin2,

Yee-Chun Chen3, Fu-Tong Liu4 and Betty A. Wu-Hsieh1*

Abstract

Invasive candidiasis is a leading cause of nosocomial bloodstream infection. Neutrophils are the important effector cells in host

resistance to candidiasis. To investigate the modulation of neutrophil fungicidal function will advance our knowledge on the control

of candidiasis. While recombinant galectin-3 enhances neutrophil phagocytosis of Candida, we found that intracellular galectin-3

downregulates neutrophil fungicidal functions. Co-immunoprecipitation and immunofluorescence staining reveal that cytosolic gal3

physically interacts with Syk in neutrophils after Candida stimulation. Gal3−/− neutrophils have higher level of Syk activation as

well as greater abilities to generate reactive oxygen species (ROS) and kill Candida than gal3+/+ cells. While galectin-3

deficiency modulates neutrophil and macrophage activation and the recruitment of monocytes and dendritic cells, the deficiency

does not affect the numbers of infiltrating neutrophils or macrophages. Galectin-3 deficiency ameliorates systemic candidiasis by

reducing fungal burden, renal pathology, and mortality. Adoptive transfer experiments demonstrate that cell intrinsic galectin-3

negatively regulates neutrophil effector functions against candidiasis. Reducing galectin-3 expression or activity by siRNA or gal3

inhibitor TD139 enhances human neutrophil ROS production. Mice treated with TD139 have enhanced ability to clear the fungus.

Our work unravels the mechanism by which galectin-3 regulates Sykdependent neutrophil fungicidal functions and raises the

possibility that blocking gal3 in neutrophils may be a promising therapeutic strategy for treating systemic candidiasis.

Keywords: galectin-3, Candida albicans, neutrophil, reactive oxygen species, Syk kinase, TD139, M2 macrophage,

monocyte/dendritic cell recruitment

Front. Immunol., 03 February 2017