Negative regulation of bacterial killing and inflammation by two novel CD16 ligands

• Published in: European journal of immunology 2016-08, Vol.46 (8), p.1926-1935
• Main Authors: Beppler, Jaqueline, Mkaddem, Sanae Ben, Michaloski, Jussara, Honorato, Rodrigo Vargas, Velasco, Irineu Tadeu, Oliveira, Paulo Sérgio Lopes, Giordano, Ricardo José, Monteiro, Renato C., Pinheiro da Silva, Fabiano
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Bacterial - immunology; Bacteria; CD16; CD16 antigen; Clearing; E coli; Escherichia coli; Escherichia coli Infections - immunology; Escherichia coli Proteins - immunology; Fc receptors; Humans; Immunoreceptor tyrosine-based activation motif; Immunotherapy; Inflammation; ITAM; Ligands; Membrane Transport Proteins - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Peptide Library; Peptides; Phage display; Phagocytes; Phagocytes - immunology; Phagocytosis; Receptors, IgG - immunology; Sepsis; Sepsis - prevention & control; Signal Transduction; Tyrosine
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201546118

Sepsis, a leading cause of death worldwide, involves exacerbated proinflammatory responses and inefficient bacterial clearance. Phagocytic cells play a crucial part in the prevention of sepsis by clearing bacteria through host innate receptors. Here, we used a phage display library to identify two peptides in Escherichia coli that interact with host innate receptors. One of these peptides, encoded by the wzxE gene of E. coli K‐12, was involved in the transbilayer movement of a trisaccharide‐lipid intermediate in the assembly of enterobacterial common antigen. Peptide‐receptor interactions induced CD16‐mediated inhibitory immunoreceptor tyrosine‐based activating motif signaling, blocking the production of ROS and bacterial killing. This CD16‐mediated inhibitory signaling was abrogated in a WzxE−/− mutant of E. coli K‐12, restoring the production of ROS and bacterial killing. Taken together, the two novel CD16 ligands identified negatively regulate bacterial killing and inflammation. Our findings may contribute toward the development of new immunotherapies for E. coli‐mediated infectious diseases and inflammation. Escherichia coli manipulates CD16 signaling to evade the immune system. Using the phage display technology, we have identified two peptides that bind to CD16. Bioinformatic analysis put in evidence that these peptides show similarity with fragments of WzXE, a protein from E. coli. These peptides have therapeutic potential for the development of novel drugs for the treatment of E. coli infections.