title: Negative regulation of bacterial killing and inflammation by two novel CD16 ligands.
abstract: 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.
authors.affiliation: Emergency Medicine Department, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Jaqueline
authors.initials: J
authors.lastname: Beppler
authors.affiliation: Inserm Unit 1149 and ERL CNRS 8252, Center for Research on Inflammation, University Paris Diderot, Paris, France.
authors.forename: Sanae Ben
authors.initials: SB
authors.lastname: Mkaddem
authors.affiliation: Vascular Biology Laboratory, Chemistry Institute, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Jussara
authors.initials: J
authors.lastname: Michaloski
authors.affiliation: Biosciences National Laboratory (LNBio), Campinas, Sao Paulo, Brazil.
authors.forename: Rodrigo Vargas
authors.initials: RV
authors.lastname: Honorato
authors.affiliation: Emergency Medicine Department, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Irineu Tadeu
authors.initials: IT
authors.lastname: Velasco
authors.affiliation: Biosciences National Laboratory (LNBio), Campinas, Sao Paulo, Brazil.
authors.forename: Paulo Sérgio Lopes
authors.initials: PS
authors.lastname: de Oliveira
authors.affiliation: Vascular Biology Laboratory, Chemistry Institute, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Ricardo José
authors.initials: RJ
authors.lastname: Giordano
authors.affiliation: Inserm Unit 1149 and ERL CNRS 8252, Center for Research on Inflammation, University Paris Diderot, Paris, France.
authors.forename: Renato C
authors.initials: RC
authors.lastname: Monteiro
authors.affiliation: Emergency Medicine Department, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Fabiano
authors.initials: F
authors.lastname: Pinheiro da Silva
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000276:immunology*; D029968:Escherichia coli Proteins / Q000276:immunology*; D006801:Humans; D008024:Ligands; D026901:Membrane Transport Proteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019151:Peptide Library; D010586:Phagocytes / Q000276:immunology; D010587:Phagocytosis; D017452:Receptors, IgG / Q000276:immunology*; D018805:Sepsis / Q000517:prevention & control; D015398:Signal Transduction
chemical_list: D000942:Antigens, Bacterial; D029968:Escherichia coli Proteins; D008024:Ligands; D026901:Membrane Transport Proteins; D019151:Peptide Library; D017452:Receptors, IgG; C475086:WzxE protein, E coli; C017286:enterobacterial common antigen
keywords: CD16; Escherichia coli; Fc receptors; ITAM; Immunotherapy; Inflammation; Phagocytosis; Sepsis