Gut Microbiota Has a Crucial Role in the Development of Hypertension and Vascular Dysfunction in Toll-like Receptor 7-Driven Lupus Autoimmunity
Metadatos
Afficher la notice complèteAuteur
de la Visitación, Néstor; Robles Vera, Iñaki; Moleón Moya, Javier; González Correa, Cristina; Aguilera Sánchez, Nazareth; Gómez Guzmán, Manuel; Sánchez Santos, Manuel; Jiménez Moleón, Rosario; Martín Morales, Natividad; O'Valle Ravassa, Francisco Javier; Romero Pérez, Miguel; Duarte Pérez, Juan ManuelEditorial
MDPI
Materia
Hypertension Endothelial Dysfunction Gut dysbiosis Immune system Systemic lupus erythematosus TLR7 activation
Date
2021Referencia bibliográfica
de la Visitación, N.; Robles-Vera, I.; Moleón, J.; González-Correa, C.; Aguilera-Sánchez, N.; Toral, M.; Gómez-Guzmán, M.; Sánchez, M.; Jiménez, R.; Martin-Morales, N.; et al. Gut Microbiota Has a Crucial Role in the Development of Hypertension and Vascular Dysfunction in Toll-like Receptor 7-Driven Lupus Autoimmunity. Antioxidants 2021, 10, 1426. https://doi.org/10.3390/ antiox10091426
Patrocinador
Comisión Interministerial de Ciencia y Tecnología, Ministerio de Economía y competitividad (MINECO) (SAF2017-84894-R, PID2020-116347RBI00); Junta de Andalucía (CTS 164, P20_00193) with funds from the European Union, and by the Ministerio de Economia y Competitividad, Instituto de Salud Carlos III (CIBER-CV); Instituto de Salud Carlos III (Sara Borrell Program); MINECO; European Union (Fondo Europeo de Desarrollo Regional, FEDER)Résumé
Our group has investigated the involvement of gut microbiota in hypertension in a murine
model of systemic lupus erythematosus induced by Toll-like receptor (TLR)-7 activation. Female
BALB/c mice were randomly assigned to four experimental groups: an untreated control (CTR), a
group treated with the TLR7 agonist imiquimod (IMQ), IMQ-treated with vancomycin, and IMQtreated with a cocktail of broad-spectrum antibiotics. We carried out faecal microbiota transplant
(FMT) from donor CTR or IMQ mice to recipient IMQ or CTR animals, respectively. Vancomycin
inhibited the increase in blood pressure; improved kidney injury, endothelial function, and oxidative
stress; and reduced T helper (Th)17 infiltration in aortas from IMQ-treated mice. The rise in blood
pressure and vascular complications present in IMQ mice were also observed in the CTR mice
recipients of IMQ microbiota. Reduced relative populations of Sutterella and Anaerovibrio were
associated with high blood pressure in our animals, which were increased after stool transplantation
of healthy microbiota to IMQ mice. The reduced endothelium-dependent vasodilator responses
to acetylcholine induced by IMQ microbiota were normalized after interleukin-17 neutralization.
In conclusion, gut microbiota plays a role in the TLR7-driven increase in Th17 cell, endothelial
dysfunction, vascular inflammation, and hypertension. The vascular changes induced by IMQ
microbiota were initiated by Th17 infiltrating the vasculature.