RT Journal Article
T1 Protective Effects of Human and Mouse Soluble Scavenger-Like CD6 Lymphocyte Receptor in a Lethal Model of Polymicrobial Sepsis
A1 Martinez-Florensa, Mario
A1 Consuegra-Fernandez, Marta
A1 Aranda, Fernando
A1 Armiger-Borras, Noelia
A1 Di Scala, Marianna
A1 Carrasco, Esther
A1 Pachon, Jeronimo
A1 Vila, Jordi
A1 Gonzalez-Aseguinolaza, Gloria
A1 Lozano, Francisco
K1 soluble CD6
K1 cecal ligation and puncture
K1 polymicrobial peritonitis
K1 scavenger receptors
K1 sepsis
K1 septic shock
K1 adjunctive therapy
K1 T-cell-activation
K1 Pattern-recognition
K1 Binding
K1 Strategies
AB Sepsis still constitutes an unmet clinical need, which could benefit from novel adjunctive strategies to conventional antibiotic therapy. The soluble form of the scavenger-like human CD6 lymphocyte receptor (shCD6) binds to key pathogenic components from Gram-positive and-negative bacteria and shows time-and dose-dependent efficacy in mouse models of monobacterial sepsis. The objective of the present work was to demonstrate the effectiveness of infusing mouse and human sCD6 by different systemic routes, either alone or as adjunctive therapy to gold standard antibiotics, in a lethal model of polymicrobial sepsis. To this end, C57BL/6 mice undergoing high-grade septic shock induced by cecal ligation and puncture (CLP; >= 90% lethality) were infused via the intraperitoneal (i.p.) or intravenous (i.v.) route with shCD6 at different doses and time points, either alone or in combination with imipenem/cilastatin (I/C) at a dose of 33 mg/kg of body weight every 8 h. Significantly reduced mortality and proinflammatory cytokine levels were observed by i.p. infusion of a single shCD6 dose (1.25 mg/kg) 1 h pre-or post-CLP. When using the i.v. route, mice survival was significantly extended by starting shCD6 infusion at later time points post-CLP (up to 6 h after CLP). Significant adjunctive effects on mouse survival were observed by i.p. or i.v. infusion of shCD6 in combination with i.p. I/C post-CLP. Similar results were obtained in mice expressing high sustained levels (5 to 10 mu g/ml) of mouse sCD6 in serum by means of transduction with hepatotropic adeno-associated virus (AAV). Taken together, the data support the conserved antibacterial effects of human and mouse sCD6 and their use as adjunctive therapy in experimental models of complex and severe polymicrobial sepsis.
PB Amer soc microbiology
SN 0066-4804
YR 2017
FD 2017-01-01
LK http://hdl.handle.net/10668/19001
UL http://hdl.handle.net/10668/19001
LA en
DS RISalud
RD Apr 13, 2025