title: Cxcl8-l1 and Cxcl8-l2 are required in the zebrafish defense against Salmonella Typhimurium.
abstract: In recent years zebrafish has emerged as an excellent model for studying the Cxcl8 signaling pathway in inflammation elicited upon tissue damage or infection. Zebrafish has two true homologs of mammalian CXCL8, named Cxcl8-l1 and Cxcl8-l2. Previously, we have shown that in wound-associated inflammation, these chemokines are up-regulated and are relevant for neutrophil recruitment. In infections, no such knowledge is available as most studies performed on this subject in zebrafish have mainly focused on Cxcl8-l1 even though Cxcl8-l2 shares higher homology with human CXCL8. In this study, we aimed to address the biological function of both zfCxcl8s in infection to improve our understanding of their respective roles under different inflammatory conditions. Gene expression analysis first confirmed that both Cxcl8-l1 and l2 are induced upon infection or in PAMP-elicited inflammatory processes. In addition, we also found that cxcl8-deficient larvae show higher susceptibility to Salmonella enterica serovar Typhimurium (S. Typhimurium) infection, reduced neutrophil recruitment to the infection site assayed in the line Tg(mpx:gfp), and decreased bacterial clearance. These data indicate that both zebrafish Cxcl8s play important roles in neutrophil recruitment and in the inflammatory response elicited upon infection or tissue damage, suggesting that even though the divergence of lower vertebrates and humans from a common ancestor occurred about 450 millions years ago, the basic principles of neutrophil recruitment are apparently conserved in all vertebrates.
authors.affiliation: Departamento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain; CSaldanha Lab, Instituto de Medicina Molecular, Lisboa, Portugal; Instituto de Bioquímica, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Sofia
authors.initials: S
authors.lastname: de Oliveira
authors.affiliation: Departamento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Azucena
authors.initials: A
authors.lastname: Lopez-Muñoz
authors.affiliation: Departamento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Martínez-Navarro
authors.affiliation: Departamento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Galindo-Villegas
authors.affiliation: Departamento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain. Electronic address: vmulero@um.es.
authors.forename: Victoriano
authors.initials: V
authors.lastname: Mulero
authors.affiliation: CSaldanha Lab, Instituto de Medicina Molecular, Lisboa, Portugal; Instituto de Bioquímica, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal. Electronic address: acalado@medicina.ulisboa.pt.
authors.forename: Ângelo
authors.initials: Â
authors.lastname: Calado
mesh_terms: D000818:Animals; D060467:Disease Resistance / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression / Q000276:immunology; D055785:Gene Knockdown Techniques; D054884:Host-Pathogen Interactions / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007814:Larva / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D008856:Microscopy, Fluorescence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012486:Salmonella typhimurium / Q000276:immunology* / Q000502:physiology; D016019:Survival Analysis; D015027:Zebrafish / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D029961:Zebrafish Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: C000600527:Cxcl8-l1, zebrafish; C000600528:Cxcl8-l2, zebrafish; D016209:Interleukin-8; D029961:Zebrafish Proteins
keywords: Bacterial infection; Chemokines; Neutrophils; Tg(mpx:gfp); cxcl8