RT Journal Article
T1 Conserved bacterial-binding peptides of the scavenger-like human lymphocyte receptor CD6 protect from mouse experimental sepsis
A1 Martínez Florensa, Mario
A1 Català, Cristina
A1 Velasco de Andrés, María
A1 Cañadas Benito, Olga
A1 Fraile Ágreda, Víctor
A1 Casadó Llombart, Sergi
A1 Armiger Borràs, Noelia
A1 Consuegra Fernández, Marta
A1 Casals Carro, María Cristina
A1 Lozano, Francisco
A2 Kishore, Uday
AB 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.
PB Frontiers Media
SN 1664-3224
YR 2018
FD 2018
LK https://hdl.handle.net/20.500.14352/93723
UL https://hdl.handle.net/20.500.14352/93723
LA eng
NO Martínez-Florensa M, Català C, Velasco-de Andrés M, Cañadas O, Fraile-Ágreda V, Casadó-Llombart S, Armiger-Borràs N, Consuegra-Fernández M, Casals C, Lozano F. Conserved Bacterial-Binding Peptides of the Scavenger-Like Human Lymphocyte Receptor CD6 Protect From Mouse Experimental Sepsis. Front. Immunol. 2018 Apr 12; 9:627
NO Ministerio de Economía y Competitividad (España)
NO Instituto de Salud Carlos III
NO European Commission
NO Ministerio de Educación, Cultura y Deporte (España)
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 15 sept 2024