The Danger Signal S100B Integrates Pathogen– and Danger–Sensing Pathways to Restrain Inflammation

PLoS Pathogens

Guglielmo Sorci¹  Francesca Riuzzi¹  Luigina Romani¹  Silvia Zagarella¹  Rosario Donato¹  Pierluigi Bonifazi¹  Gloria Giovannini¹  Francesco Bistoni¹  Teresa Zelante¹ 

[1] Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy

关键词: Inflammation;    Immune receptor signaling;    Epithelial cells;    Enzyme-linked immunoassays;    Aspergillus;    Small interfering RNAs;    Immunoprecipitation;    Gene expression;   

DOI  :  10.1371/journal.ppat.1001315

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Humans inhale hundreds of Aspergillus conidia without adverse consequences. Powerful protective mechanisms may ensure prompt control of the pathogen and inflammation. Here we reveal a previously unknown mechanism by which the danger molecule S100B integrates pathogen– and danger–sensing pathways to restrain inflammation. Upon forming complexes with TLR2 ligands, S100B inhibited TLR2 via RAGE, through a paracrine epithelial cells/neutrophil circuit that restrained pathogen-induced inflammation. However, upon binding to nucleic acids, S100B activated intracellular TLRs eventually resolve danger-induced inflammation via transcriptional inhibition of S100B. Thus, the spatiotemporal regulation of TLRs and RAGE by S100B provides evidence for an evolving braking circuit in infection whereby an endogenous danger protects against pathogen–induced inflammation and a pathogen–sensing mechanism resolves danger–induced inflammation.

【 授权许可】

CC BY