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Title: | Conserved bacterial-binding peptides of the scavenger-like lymphocyte receptor CD6 protect from mouse experimental sepsis |
Author: | Martínez-Florensa, Mario Català, Cristina Velasco de Andrés, María Cañadas, Olga Fraile Ágreada, Víctor Casadó Llombart, Sergi Armiger Borràs, Noelia Consuegra-Fernández, Marta Casals, Cristina Lozano Soto, Francisco |
Keywords: | Septicèmia Immunitat Cisteïna Septicemia Immunity Cysteine |
Issue Date: | 12-Apr-2018 |
Publisher: | Frontiers Media |
Abstract: | Sepsis is an unmet clinical need constituting one of the most important causes of death worldwide, a fact aggravated by the appearance of multidrug resistant strains due to indiscriminate use of antibiotics. Host innate immune receptors involved in pathogen-associated molecular patterns (PAMPs) recognition represent a source of broad-spectrum therapies alternative or adjunctive to antibiotics. Among the few members of the ancient and highly conserved scavenger receptor cysteine-rich superfamily (SRCR-SF) sharing bacterial-binding properties there is CD6, a lymphocyte-specific surface receptor. Here, we analyze the bacterial-binding properties of three conserved short peptides (11-mer) mapping at extracellular SRCR domains of human CD6 (CD6.PD1, GTVEVRLEASW; CD6.PD2 GRVEMLEHGEW; and CD6.PD3, GQVEVHFRGVW). All peptides show high binding affinity for PAMPs from Gram-negative (lipopolysaccharide; Kd from 3.5 to 3,000 nM) and Gram-positive (lipoteichoic acid; Kd from 36 to 680 nM) bacteria. The CD6.PD3 peptide possesses broad bacterial-agglutination properties and improved survival of mice undergoing polymicrobial sepsis in a dose- and time-dependent manner. Accordingly, CD6.PD3 triggers a decrease in serum levels of both pro-inflammatory cytokines and bacterial load. Interestingly, CD6.PD3 shows additive survival effects on septic mice when combined with Imipenem/Cilastatin. These results illustrate the therapeutic potential of peptides retaining the bacterial-binding properties of native CD6. |
Note: | Reproducció del document publicat a: https://doi.org/10.3389/fimmu.2018.00627 |
It is part of: | Frontiers in Immunology, 2018, vol. 9, p. 627 |
URI: | http://hdl.handle.net/2445/176615 |
Related resource: | https://doi.org/10.3389/fimmu.2018.00627 |
ISSN: | 1664-3224 |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Biomedicina) |
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