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2018-04-12

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cc-by (c) Martínez Florensa, Mario et al., 2018
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/176615

Conserved bacterial-binding peptides of the scavenger-like lymphocyte receptor CD6 protect from mouse experimental sepsis

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https://doi.org/10.3389/fimmu.2018.00627

Resum

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.

Matèries

Septicèmia, Immunitat, Cisteïna

Matèries (anglès)

Septicemia, Immunity, Cysteine

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Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

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. Conserved bacterial-binding peptides of the scavenger-like lymphocyte receptor CD6 protect from mouse experimental sepsis. _Frontiers in Immunology_. 2018. Vol. 9, núm. 627. [consulta: 24 de gener de 2026]. ISSN: 1664-3224. [Disponible a: https://hdl.handle.net/2445/176615]

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