SIGNR3‐dependent immune regulation by Lactobacillus acidophilus surface layer protein A in colitis. (9th February 2015)

• Record Type: Journal Article
• Authors: Lightfoot, Yaíma L; Selle, Kurt; Yang, Tao; Goh, Yong Jun; Sahay, Bikash; Zadeh, Mojgan; Owen, Jennifer L; Colliou, Natacha; Li, Eric; Johannssen, Timo; Lepenies, Bernd; Klaenhammer, Todd R; Mohamadzadeh, Mansour
• Is Part Of: EMBO journal. Volume 34:Number 7(2015)
• Page Start: 881
• Page End: 895
• Publication Date: 2015-02-09
• Subjects: Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.201490296
• Languages: English
• ISSNs: 0261-4189

Abstract

<abstract abstract-type="main" id="embj201490296-abs-0001"> <title>Abstract</title> <p>Intestinal immune regulatory signals govern gut homeostasis. Breakdown of such regulatory mechanisms may result in inflammatory bowel disease (IBD). <italic>Lactobacillus acidophilus</italic> 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 <italic>Signr3</italic>^{<italic>−/−</italic>} 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.</p> </abstract>