title: TLR agonists extend the functional lifespan of professional phagocytic granulocytes in the bony fish gilthead seabream and direct precursor differentiation towards the production of granulocytes.
abstract: Neutrophils are major cells participants in innate host responses. They are short-lived leukocytes, although microbial products activate intracellular signaling cascades that prolong their survival by inhibiting constitutive apoptosis. To gain insight into the phylogeny of this important cell type, we examined the ability of toll-like receptor agonists to extend the lifespan of gilthead seabream (Sparus aurata L.) acidophilic granulocytes, which are the functional equivalent of mammalian neutrophils. The results obtained demonstrated that apoptosis was also the default state of seabream acidophilic granulocytes and that toll-like receptor agonists were able to dramatically extend their functional lifespan (up to 10 days) by inhibiting apoptosis and inducing a long lasting activation of phagocytic and respiratory burst activities, together with the expression of genes coding for several proinflammatory molecules. This process was independent on contaminating cells and interleukin-1β production. In addition, the results showed that p38 mitogen-activated protein kinase, but not nuclear factor κB, c-Jun terminal kinase or phosphatidylinositol 3-kinase, was involved in the inhibition of acidophilic granulocyte apoptosis following toll-like receptor engagement. Finally, stimulation of head kidney hematopoietic precursor cells with toll-like receptor agonists promoted their terminal differentiation to acidophilic granulocytes. These results demonstrated that the extension of neutrophil lifespan by microbial products is conserved in lower vertebrates although the magnitude of the response is much higher in fish.
authors.affiliation: Department of Cell Biology and Histology, Faculty of Biology, University of Murcia, Campus Universitario de Espinardo, 30100 Murcia, Spain.
authors.forename: María P
authors.initials: MP
authors.lastname: Sepulcre
authors.forename: Azucena
authors.initials: A
authors.lastname: López-Muñoz
authors.forename: Diego
authors.initials: D
authors.lastname: Angosto
authors.forename: Alicia
authors.initials: A
authors.lastname: García-Alcazar
authors.forename: José
authors.initials: J
authors.lastname: Meseguer
authors.forename: Victoriano
authors.initials: V
authors.lastname: Mulero
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005408:Flagellin / Q000494:pharmacology; D020869:Gene Expression Profiling; D006098:Granulocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D057809:HEK293 Cells; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007668:Kidney / Q000166:cytology; D016328:NF-kappa B / Q000378:metabolism; D010586:Phagocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D021541:Sea Bream / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000819:agonists*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D016328:NF-kappa B; D051193:Toll-Like Receptors; D005408:Flagellin; D019869:Phosphatidylinositol 3-Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases