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Candel Camacho, Sergio

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Candel Camacho, Sergio
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Universidad de Murcia. Departamento de Biología Celular e Histología
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2013 - 20163
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    Neutrophils mediate Salmonella Typhimurium clearance through the GBP4 inflammasome-dependent production of prostaglandins
    (Nature Research, 2016-07-01) Martín Sánchez, María Rosario Fátima; Tyrkalska, Sylwia D.; Candel Camacho, Sergio; Angosto, Diego; Gómez Abellán, Victoria; García Moreno, Diana; Zapata Pérez, Rubén; Sánchez Ferrer, Álvaro; Pelegrín Vivancos, Pablo; Mulero Méndez, Victoriano Francisco; Sepulcre Cortés, María Pilar; Farmacología
    Inflammasomes are cytosolic molecular platforms that alert the immune system about thepresence of infection. Here we report that zebrafish guanylate-binding protein 4 (Gbp4),an IFNg-inducible GTPase protein harbouring a C-terminal CARD domain, is required for theinflammasome-dependent clearance of Salmonella Typhimurium (ST) by neutrophils in vivo.Despite the presence of the CARD domain, Gbp4 requires the universal inflammasomeadaptor Asc for mediating its antibacterial function. In addition, the GTPase activity of Gbp4is indispensable for inflammasome activation and ST clearance. Mechanistically, neutrophilsare recruited to the infection site through the inflammasome-independent production of thechemokine (CXC motif) ligand 8 and leukotriene B4, and then mediate bacterial clearancethrough the Gbp4 inflammasome-dependent biosynthesis of prostaglandin D2. Our resultspoint to GBPs as key inflammasome adaptors required for prostaglandin biosynthesis andbacterial clearance by neutrophils and suggest that transient activation of the inflammasomemay be used to treat bacterial infections.
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    TNFα Impairs Rhabdoviral Clearance by Inhibiting the Host Autophagic Antiviral Response
    (Public Library of Science, 2016-06-28) Raquel Espín-Palazón; Espín Palazón, Raquel; Martínez López, Alicia; Roca Soler, Francisco José; López Muñoz, Azucena; Tyrkalska, Syilwia Dominika; Candel Camacho, Sergio; García Moreno, Diana; Falco, Alberto; Meseguer, José; Estepa, Amparo; Mulero Méndez, Victoriano Francisco; Biología Celular e Histología
    TNFα is a pleiotropic pro-inflammatory cytokine with a key role in the activation of the immune system to fight viral infections. Despite its antiviral role, a few viruses might utilize the host produced TNFα to their benefit. Some recent reports have shown that anti-TNFα therapies could be utilized to treat certain viral infections. However, the underlying mechanisms by which TNFα can favor virus replication have not been identified. Here, a rhabdoviral infection model in zebrafish allowed us to identify the mechanism of action by which Tnfa has a deleterious role for the host to combat certain viral infections. Our results demonstrate that Tnfa signals through its receptor Tnfr2 to enhance viral replication. Mechanistically, Tnfa does not affect viral adhesion and delivery from endosomes to the cytosol. In addition, the host interferon response was also unaffected by Tnfa levels. However, Tnfa blocks the host autophagic response, which is required for viral clearance. This mechanism of action provides new therapeutic targets for the treatment of SVCV-infected fish, and advances our understanding of the previously enigmatic deleterious role of TNFα in certain viral infections.
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    TNF receptors regulate vascular homeostasis in zebrafish through a caspase-8, caspase-2 and P53 apoptotic program that bypasses caspase-3
    (The Company of Biologists, 2013-03-01) Espín, Raquel; Roca Soler, Francisco José; Candel Camacho, Sergio; Sepulcre Cortés, María Pilar; González Rosa, Juan M.; Alcaraz Pérez, Francisca; Meseguer, José; Cayuela, María L.; Mercader, Nadia; Mulero Méndez, Victoriano Francisco; Biología Celular e Histología
    Although it is known that tumor necrosis factor receptor (TNFR) signaling plays a crucial role in vascular integrity and homeostasis, the contribution of each receptor to these processes and the signaling pathway involved are still largely unknown. Here, we show that targeted gene knockdown of TNFRSF1B in zebrafish embryos results in the induction of a caspase-8, caspase-2 and P53-dependent apoptotic program in endothelial cells that bypasses caspase-3. Furthermore, the simultaneous depletion of TNFRSF1A or the activation of NF-κB rescue endothelial cell apoptosis, indicating that a signaling balance between both TNFRs is required for endothelial cell integrity. In endothelial cells, TNFRSF1A signals apoptosis through caspase-8, whereas TNFRSF1B signals survival via NF-κB. Similarly, TNFα promotes the apoptosis of human endothelial cells through TNFRSF1A and triggers caspase-2 and P53 activation. We have identified an evolutionarily conserved apoptotic pathway involved in vascular homeostasis that provides new therapeutic targets for the control of inflammation- and tumor-driven angiogenesis.
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