title: Targeting of key pathogenic factors from gram-positive bacteria by the soluble ectodomain of the scavenger-like lymphocyte receptor CD6.
abstract: Gram-positive bacteria cause a broad spectrum of infection-related diseases in both immunocompetent and immunocompromised hosts, ranging from localized infections to severe systemic conditions such as septic and toxic shock syndromes. This situation has been aggravated by the recent emergence of multidrug-resistant strains, thus stressing the need for alternative therapeutic approaches. One such possibility would be modulating the host's immune response. Herein, the potential use of a soluble form of the scavenger-like human lymphocyte receptor CD6 (shCD6) belonging to an ancient family of innate immune receptors has been evaluated. shCD6 can bind to a broad spectrum of gram-positive bacteria thanks to the recognition of highly conserved cell wall components (lipoteichoic acid [LTA] and peptidoglycan [PGN]), which are essential for their viability and pathogenicity and are not amenable to antibiotic resistance. shCD6 has in vitro inhibitory effects on both bacterial growth and Toll-like receptor-mediated inflammatory response induced by LTA plus PGN. In vivo infusion of shCD6 improves survival on mouse models of septic shock by Staphylococcus aureus (either multidrug-resistant or -sensitive) or their endotoxins (LTA + PGN) or exotoxins (TSST-1). These results support the use of shCD6 and/or other scavenger-like immune receptors in the treatment of severe gram-positive-induced infectious conditions.
authors.affiliation: Grup d'Immunorreceptors, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centre Esther Koplowitz.
authors.forename: Mario
authors.initials: M
authors.lastname: Martínez-Florensa
authors.forename: Marta
authors.initials: M
authors.lastname: Consuegra-Fernández
authors.forename: Vanesa G
authors.initials: VG
authors.lastname: Martínez
authors.forename: Olga
authors.initials: O
authors.lastname: Cañadas
authors.forename: Noelia
authors.initials: N
authors.lastname: Armiger-Borràs
authors.forename: Lizette
authors.initials: L
authors.lastname: Bonet-Roselló
authors.forename: Aina
authors.initials: A
authors.lastname: Farrán
authors.forename: Jordi
authors.initials: J
authors.lastname: Vila
authors.forename: Cristina
authors.initials: C
authors.lastname: Casals
authors.forename: Francisco
authors.initials: F
authors.lastname: Lozano
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology* / Q000627:therapeutic use; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology* / Q000627:therapeutic use; D001688:Biological Products / Q000276:immunology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010457:Peptidoglycan / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding; D012772:Shock, Septic / Q000188:drug therapy; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000276:immunology*; D013682:Teichoic Acids / Q000276:immunology* / Q000378:metabolism; D037521:Virulence Factors / Q000276:immunology* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D001688:Biological Products; C062279:CD6 antigen; D010457:Peptidoglycan; D013682:Teichoic Acids; D037521:Virulence Factors
keywords: CD6; Staphylococcus aureus; gram-positive bacteria; lipoteichoic acid; peptidoglycan; scavenger receptors; sepsis; superantigens; toxic shock