Yaíma L Lightfoot, Kurt Selle, Tao Yang, Yong Jun Goh, Bikash Sahay, Mojgan Zadeh, Jennifer L Owen, Natacha Colliou, Eric Li, Timo Johannssen, Bernd Lepenies, Todd R Klaenhammer, Mansour Mohamadzadeh
The EMBO journal 2015 Apr 1Intestinal immune regulatory signals govern gut homeostasis. Breakdown of such regulatory mechanisms may result in inflammatory bowel disease (IBD). Lactobacillus acidophilus contains unique surface layer proteins (Slps), including SlpA, SlpB, SlpX, and lipoteichoic acid (LTA), which interact with pattern recognition receptors to mobilize immune responses. Here, to elucidate the role of SlpA in protective immune regulation, the NCK2187 strain, which solely expresses SlpA, was generated. NCK2187 and its purified SlpA bind to the C-type lectin SIGNR3 to exert regulatory signals that result in mitigation of colitis, maintenance of healthy gastrointestinal microbiota, and protected gut mucosal barrier function. However, such protection was not observed in Signr3(-/-) mice, suggesting that the SlpA/SIGNR3 interaction plays a key regulatory role in colitis. Our work presents critical insights into SlpA/SIGNR3-induced responses that are integral to the potential development of novel biological therapies for autoinflammatory diseases, including IBD. © 2015 The Authors.
Yaíma L Lightfoot, Kurt Selle, Tao Yang, Yong Jun Goh, Bikash Sahay, Mojgan Zadeh, Jennifer L Owen, Natacha Colliou, Eric Li, Timo Johannssen, Bernd Lepenies, Todd R Klaenhammer, Mansour Mohamadzadeh. SIGNR3-dependent immune regulation by Lactobacillus acidophilus surface layer protein A in colitis. The EMBO journal. 2015 Apr 1;34(7):881-95
PMID: 25666591
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