title: Transient infection of the zebrafish notochord with E. coli induces chronic inflammation.
abstract: Zebrafish embryos and larvae are now well-established models in which to study infectious diseases. Infections with non-pathogenic Gram-negative Escherichia coli induce a strong and reproducible inflammatory response. Here, we study the cellular response of zebrafish larvae when E. coli bacteria are injected into the notochord and describe the effects. First, we provide direct evidence that the notochord is a unique organ that is inaccessible to leukocytes (macrophages and neutrophils) during the early stages of inflammation. Second, we show that notochord infection induces a host response that is characterised by rapid clearance of the bacteria, strong leukocyte recruitment around the notochord and prolonged inflammation that lasts several days after bacteria clearance. During this inflammatory response, il1b is first expressed in macrophages and subsequently at high levels in neutrophils. Moreover, knock down of il1b alters the recruitment of neutrophils to the notochord, demonstrating the important role of this cytokine in the maintenance of inflammation in the notochord. Eventually, infection of the notochord induces severe defects of the notochord that correlate with neutrophil degranulation occurring around this tissue. This is the first in vivo evidence that neutrophils can degranulate in the absence of a direct encounter with a pathogen. Persistent inflammation, neutrophil infiltration and restructuring of the extracellular matrix are defects that resemble those seen in bone infection and in some chondropathies. As the notochord is a transient embryonic structure that is closely related to cartilage and bone and that contributes to vertebral column formation, we propose infection of the notochord in zebrafish larvae as a new model to study the cellular and molecular mechanisms underlying cartilage and bone inflammation.
authors: Dynamique des Interactions Membranaires Normales et Pathologiques, Université Montpellier 2, UMR 5235, case 107, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France. CNRS; UMR 5235, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France. mai.nguyen-chi@univ-montp2.fr lutfalla@univ-montp2.fr.
authors: Mai
authors: M
authors: Nguyen-Chi
authors: Dynamique des Interactions Membranaires Normales et Pathologiques, Université Montpellier 2, UMR 5235, case 107, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France. CNRS; UMR 5235, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France.
authors: Quang Tien
authors: QT
authors: Phan
authors: Dynamique des Interactions Membranaires Normales et Pathologiques, Université Montpellier 2, UMR 5235, case 107, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France. CNRS; UMR 5235, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France.
authors: Catherine
authors: C
authors: Gonzalez
authors: Dynamique des Interactions Membranaires Normales et Pathologiques, Université Montpellier 2, UMR 5235, case 107, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France. CNRS; UMR 5235, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France.
authors: Jean-François
authors: JF
authors: Dubremetz
authors: Macrophages et Développement de l'Immunité, Institut Pasteur, Paris F-75015, France. CNRS URA2578, Paris F-75015, France.
authors: Jean-Pierre
authors: JP
authors: Levraud
authors: Macrophages et Développement de l'Immunité, Institut Pasteur, Paris F-75015, France. CNRS URA2578, Paris F-75015, France. mai.nguyen-chi@univ-montp2.fr lutfalla@univ-montp2.fr.
authors: Georges
authors: G
authors: Lutfalla
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004625:Embryo, Nonmammalian / Q000382:microbiology / Q000473:pathology; D004926:Escherichia coli / Q000502:physiology* / Q000648:ultrastructure; D004927:Escherichia coli Infections / Q000196:embryology* / Q000382:microbiology / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007249:Inflammation / Q000382:microbiology / Q000473:pathology*; D053583:Interleukin-1beta / Q000378:metabolism; D007814:Larva / Q000382:microbiology / Q000648:ultrastructure; D008264:Macrophages / Q000473:pathology; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000473:pathology; D009672:Notochord / Q000382:microbiology* / Q000473:pathology* / Q000648:ultrastructure; D010587:Phagocytosis; D013131:Spine / Q000196:embryology / Q000473:pathology; D015027:Zebrafish / Q000196:embryology* / Q000382:microbiology*
chemical_list: D053583:Interleukin-1beta; D049452:Green Fluorescent Proteins
keywords: Inflammation; Interleukin-1β; Neutrophils; Zebrafish