Evolution of Lipopolysaccharide (LPS) Recognition and Signaling: Fish TLR4 Does Not Recognize LPS and Negatively Regulates NF-κB Activation

Alcaraz-Perez, Francisca; López-Muñoz, Azucena; Meseguer Peñalver, J.; Cayuela Fuentes, Maria Luisa; Mulero Méndez, Victoriano Francisco; Sepulcre Cortés, María Pilar; Roca Soler, Francisco José

Publication:
Evolution of Lipopolysaccharide (LPS) Recognition and Signaling: Fish TLR4 Does Not Recognize LPS and Negatively Regulates NF-κB Activation

dc.contributor.author	Alcaraz-Perez, Francisca
dc.contributor.author	López-Muñoz, Azucena
dc.contributor.author	Meseguer Peñalver, J.
dc.contributor.author	Cayuela Fuentes, Maria Luisa
dc.contributor.author	Mulero Méndez, Victoriano Francisco
dc.contributor.author	Sepulcre Cortés, María Pilar
dc.contributor.author	Roca Soler, Francisco José
dc.contributor.department	Bioquímica y Biología Molecular B e Inmunología
dc.date.accessioned	2025-01-29T16:36:31Z
dc.date.available	2025-01-29T16:36:31Z
dc.date.issued	2009-02-15
dc.description	© 2009 by The American Association of Immunologists This document is the published version of a published work that appeared in final form in Journal of Immunology To access the final edited and published work see: https://doi.org/10.4049/jimmunol.0801755
dc.description.abstract	It has long been established that lower vertebrates, most notably fish and amphibians, are resistant to the toxic effect of LPS. Furthermore, the lack of a TLR4 ortholog in some fish species and the lack of the essential costimulatory molecules for LPS activation via TLR4 (i.e., myeloid differentiation protein 2 (MD-2) and CD14) in all the fish genomes and expressed sequence tag databases available led us to hypothesize that the mechanism of LPS recognition in fish may be different from that of mammals. To shed light on the role of fish TLRs in LPS recognition, a dual-luciferase reporter assay to study NF-κB activation in whole zebrafish embryos was developed and three different bony fish models were studied: 1) the gilthead seabream (Sparus aurata, Perciformes), an immunological-tractable teleost model in which the presence of a TLR4 ortholog is unknown; 2) the spotted green pufferfish (Tetraodon nigroviridis, Tetraodontiformes), which lacks a TLR4 ortholog; and 3) the zebrafish (Danio rerio, Cypriniformes), which possesses two TLR4 orthologs. Our results show that LPS signaled via a TLR4- and MyD88-independent manner in fish, and, surprisingly, that the zebrafish TLR4 orthologs negatively regulated the MyD88-dependent signaling pathway. We think that the identification of TLR4 as a negative regulator of TLR signaling in the zebrafish, together with the absence of this receptor in most fish species, explains the resistance of fish to endotoxic shock and supports the idea that the TLR4 receptor complex for LPS recognition arose after the divergence of fish and tetrapods.	es
dc.format	application/pdf	es
dc.format.extent	11	es
dc.identifier.citation	Journal of Immunology, Volume 182, Issue 4, 2009, Pages 1836-1845
dc.identifier.doi	https://doi.org/10.4049/jimmunol.0801755
dc.identifier.issn	Print.: 0022-1767
dc.identifier.issn	Electronic.: 1550-6606
dc.identifier.uri	http://hdl.handle.net/10201/149668
dc.language	eng	es
dc.publisher	American Association of Immunologists Oxford University Press	es
dc.relation	Spanish Ministry of Education and Science (Grants BIO2005-05078 and CSD2007-00002 to V.M.), the Sixth Framework Programme of the European Union (Grant FOOD-CT-2005-007103 to V.M.), the Spanish Ministry of Health (Grant PI060369 to M.L.C.), and the University of Murcia (fellowships to F.A.-P. and A.L.-M.)	es
dc.relation.publisherversion	https://journals.aai.org/jimmunol/article/182/4/1836/104035/Evolution-of-Lipopolysaccharide-LPS-Recognition
dc.rights	info:eu-repo/semantics/restrictedAccess	es
dc.subject	TLR	es
dc.subject	LPS	es
dc.subject	Teleosts	es
dc.subject	Fish	es
dc.subject	Immune response	es
dc.subject.other	CDU::5 - Ciencias puras y naturales::57 - Biología::577 - Bioquímica. Biología molecular. Biofísica	es
dc.title	Evolution of Lipopolysaccharide (LPS) Recognition and Signaling: Fish TLR4 Does Not Recognize LPS and Negatively Regulates NF-κB Activation	es
dc.type	info:eu-repo/semantics/article	es
dspace.entity.type	Publication	es
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