2. Academic Validation
  3. A small secreted protein triggers a TLR2/4-dependent inflammatory response during invasive Candida albicans infection

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

  • Nat Commun. 2019 Mar 4;10(1):1015. doi: 10.1038/s41467-019-08950-3.
Wenjuan Wang 1,  Zihou Deng 2,  Hongyu Wu 1,  Qun Zhao 1,  Tiantian Li 2,  Wencheng Zhu 1,  Xiongjun Wang 1,  Longhai Tang 3,  Chengshu Wang 4,  Shu-Zhong Cui 5,  Hui Xiao 6,  Jiangye Chen 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China.
  • 2 CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, CAS Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China.
  • 3 Suzhou Blood Center, Suzhou, Jiangsu, 215000, China.
  • 4 CAS Key Laboratory of Insect Developmental and Evolutionary Biology, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, 200032, China.
  • 5 State Key Laboratory of Respiratory Diseases, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510095, China.
  • 6 CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, CAS Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China. [email protected].
  • 7 State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China. [email protected].
PMID: 30833559 DOI: 10.1038/s41467-019-08950-3
Abstract

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-κB 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.

Figures
Products