title: SIGNR3-dependent immune regulation by Lactobacillus acidophilus surface layer protein A in colitis.
abstract: Intestinal 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.
authors: Department of Infectious Diseases and Pathology, University of Florida, Gainesville, FL, USA Division of Gastroenterology, Hepatology & Nutrition, Department of Medicine, University of Florida, Gainesville, FL, USA.
authors: Yaíma L
authors: YL
authors: Lightfoot
authors: Department of Food, Bioprocessing and Nutrition Sciences, and Genomic Sciences Program, North Carolina State University, Raleigh, NC, USA.
authors: Kurt
authors: K
authors: Selle
authors: Department of Infectious Diseases and Pathology, University of Florida, Gainesville, FL, USA Division of Gastroenterology, Hepatology & Nutrition, Department of Medicine, University of Florida, Gainesville, FL, USA.
authors: Tao
authors: T
authors: Yang
authors: Department of Food, Bioprocessing and Nutrition Sciences, and Genomic Sciences Program, North Carolina State University, Raleigh, NC, USA.
authors: Yong Jun
authors: YJ
authors: Goh
authors: Department of Infectious Diseases and Pathology, University of Florida, Gainesville, FL, USA Division of Gastroenterology, Hepatology & Nutrition, Department of Medicine, University of Florida, Gainesville, FL, USA.
authors: Bikash
authors: B
authors: Sahay
authors: Department of Infectious Diseases and Pathology, University of Florida, Gainesville, FL, USA Division of Gastroenterology, Hepatology & Nutrition, Department of Medicine, University of Florida, Gainesville, FL, USA.
authors: Mojgan
authors: M
authors: Zadeh
authors: Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
authors: Jennifer L
authors: JL
authors: Owen
authors: Department of Infectious Diseases and Pathology, University of Florida, Gainesville, FL, USA Division of Gastroenterology, Hepatology & Nutrition, Department of Medicine, University of Florida, Gainesville, FL, USA.
authors: Natacha
authors: N
authors: Colliou
authors: Division of Infectious Diseases and Global Medicine, Department of Medicine, University of Florida, Gainesville, FL, USA.
authors: Eric
authors: E
authors: Li
authors: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany.
authors: Timo
authors: T
authors: Johannssen
authors: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany.
authors: Bernd
authors: B
authors: Lepenies
authors: Department of Food, Bioprocessing and Nutrition Sciences, and Genomic Sciences Program, North Carolina State University, Raleigh, NC, USA.
authors: Todd R
authors: TR
authors: Klaenhammer
authors: Department of Infectious Diseases and Pathology, University of Florida, Gainesville, FL, USA Division of Gastroenterology, Hepatology & Nutrition, Department of Medicine, University of Florida, Gainesville, FL, USA m.zadeh@ufl.edu.
authors: Mansour
authors: M
authors: Mohamadzadeh
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D007779:Lactobacillus acidophilus / Q000235:genetics / Q000276:immunology*; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D008070:Lipopolysaccharides / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D013682:Teichoic Acids / Q000235:genetics / Q000276:immunology
chemical_list: D015703:Antigens, CD; D001426:Bacterial Proteins; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; C494354:SIGNR3 protein, mouse; D013682:Teichoic Acids; C070683:surface layer protein A, Bacteria; C009900:lipoteichoic acid
keywords: Lactobacillus acidophilus; SIGNR3; colitis; immune regulation; surface layer protein A