Preserving Sialic Acid-dependent Pattern Recognition by CD24-Siglec G Interaction for Therapy of Polybacterial Sepsis

• Published in: Nature biotechnology 2011-04, Vol.29 (5), p.428-435
• Main Authors: Chen, Guo-Yun, Chen, Xi, King, Samantha, Cavassani, Karen A., Cheng, Jiansong, Zheng, Xincheng, Cao, Hongzhi, Yu, Hai, Qu, Jingyao, Fang, Dexing, Wu, Wei, Bai, Xue-Feng, Liu, Jin-Qing, Woodiga, Shireen A., Chen, Chong, Sun, Lei, Hogaboam, Cory M., Kunkel, Steven L., Zheng, Pan, Liu, Yang
• Format: Article
• Language: English
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/nbt.1846

Control of inflammation is critical for therapy of infectious diseases. Pathogen-associated and/or danger-associated molecular patterns (PAMPs and DAMPs, respectively) are the two major inducers of inflammation. Because the CD24-Siglec G/10 interactions selectively repress inflammatory response to DAMPs, microbial disruption of the negative regulation would provide a general mechanism to exacerbate inflammation. Here we show that the sialic acid-based pattern recognitions of CD24 by Siglec G/10 are targeted by sialidases in polybacterial sepsis. Sialidase inhibitors protect mice against sepsis by a CD24-Siglecg -dependent mechanism, whereas a targeted mutation of either CD24 or Siglecg exacerbates sepsis. Bacterial sialidase and host CD24 and Siglecg genes interact to determine pathogen virulence. Our data demonstrate a critical role for disrupting sialic acid-based pattern recognitions in microbial virulence and suggest a therapeutic approach to dampen harmful inflammatory response during infection.