A small secreted protein triggers a TLR2/4-dependent inflammatory response during invasive Candida albicans infection

被引：54

作者：

Wang, Wenjuan ^{[1
]}

Deng, Zihou ^{[2
]}

Wu, Hongyu ^{[1
]}

Zhao, Qun ^{[1
]}

Li, Tiantian ^{[2
]}

Zhu, Wencheng ^{[1
]}

Wang, Xiongjun ^{[1
]}

Tang, Longhai ^{[3
]}

Wang, Chengshu ^{[4
]}

Cui, Shu-Zhong ^{[5
]}

Xiao, Hui ^{[2
]}

Chen, Jiangye ^{[1
]}

机构：

[1] Chinese Acad Sci, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Univ Chinese Acad Sci, 320 Yue Yang Rd, Shanghai 200031, Peoples R China

[2] Chinese Acad Sci, CAS Key Lab Mol Virol & Immunol, CAS Ctr Excellence Mol Cell Sci, Inst Pasteur Shanghai,Univ Chinese Acad Sci, 320 Yue Yang Rd, Shanghai 200031, Peoples R China

[3] Suzhou Blood Ctr, Suzhou 215000, Jiangsu, Peoples R China

[4] Chinese Acad Sci, CAS Key Lab Insect Dev & Evolutionary Biol, Shanghai Inst Plant Physiol & Ecol, Shanghai 200032, Peoples R China

[5] Guangzhou Med Univ, State Key Lab Resp Dis, Affiliated Canc Hosp & Inst, Guangzhou 510095, Guangdong, Peoples R China

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

中国国家自然科学基金;

关键词：

PATTERN-RECOGNITION RECEPTOR; HOST-DEFENSE; ASPARTIC PROTEASES; NLRP3; INFLAMMASOME; VIRULENCE FACTORS; INDUCTION; INNATE; LECTIN; LIPOPOLYSACCHARIDE; DECTIN-2;

D O I：

10.1038/s41467-019-08950-3

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Candida albicans can switch from commensal to pathogenic mode, causing mucosal or disseminated candidiasis. The host relies on pattern-recognition receptors including Toll-like receptors (TLRs) and C-type lectin receptors (CLRs) to sense invading fungal pathogens and launch immune defense mechanisms. However, the complex interplay between fungus and host innate immunity remains incompletely understood. Here we report that C. albicans upregulates expression of a small secreted cysteine-rich protein Sel1 upon encountering limited nitrogen and abundant serum. Sel1 activates NF-kappa B and MAPK signaling pathways, leading to expression of proinflammatory cytokines and chemokines. Comprehensive genetic and biochemical analyses reveal both TLR2 and TLR4 are required for the recognition of Sel1. Further, SEL1-deficient C. albicans display an impaired immune response in vivo, causing increased morbidity and mortality in a bloodstream infection model. We identify a critical component in the Candida-host interaction that opens a new avenue to tackle Candida infection and inflammation.

引用

页数：14

共 65 条

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