title: A Zebrafish Model forChlamydiaInfection with the Obligate Intracellular PathogenWaddlia chondrophila.
abstract: Obligate intracellular chlamydial bacteria of the Planctomycetes-Verrucomicrobia-Chlamydiae (PVC) superphylum are important pathogens of terrestrial and marine vertebrates, yet many features of their pathogenesis and host specificity are still unknown. This is particularly true for families such as theWaddliaceawhich, in addition to epithelia, cellular targets for nearly allChlamydia, can infect and replicate in macrophages, an important arm of the innate immune system or in their free-living amoebal counterparts. An ideal pathogen model system should include both host and pathogen, which led us to develop the first larval zebrafish model for chlamydial infections withWaddlia chondrophila. By varying the means and sites of application, epithelial cells of the swim bladder, endothelial cells of the vasculature and phagocytosing cells of the innate immune system became preferred targets for infection in zebrafish larvae. Through the use of transgenic zebrafish, we could observe recruitment of neutrophils to the infection site and demonstrate for the first time thatW. chondrophilais taken up and replicates in these phagocytic cells and not only in macrophages. Furthermore, we present evidence that myeloid differentiation factor 88 (MyD88) mediated signaling plays a role in the innate immune reaction toW. chondrophila, eventually by Toll-like receptor (TLRs) recognition. Infected larvae with depleted levels of MyD88 showed a higher infection load and a lower survival rate compared to control fish. This work presents a new and potentially powerful non-mammalian experimental model to study the pathology of chlamydial virulencein vivoand opens up new possibilities for investigation of other members of the PVC superphylum.
authors.affiliation: Vetsuisse Faculty, Institute for Veterinary Pathology, University of Zurich Zurich, Switzerland.
authors.forename: Alexander G J
authors.initials: AG
authors.lastname: Fehr
authors.affiliation: Vetsuisse Faculty, Institute for Veterinary Pathology, University of Zurich Zurich, Switzerland.
authors.forename: Maja
authors.initials: M
authors.lastname: Ruetten
authors.affiliation: Vetsuisse Faculty, Institute for Veterinary Pathology, University of ZurichZurich, Switzerland; Functional Genomics Center Zurich, Molecular and Life Sciences, University of ZurichZurich, Switzerland.
authors.forename: Helena M B
authors.initials: HM
authors.lastname: Seth-Smith
authors.affiliation: Vetsuisse Faculty, Institute for Veterinary Pathology, University of Zurich Zurich, Switzerland.
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Nufer
authors.affiliation: Vetsuisse Faculty, Institute of Veterinary Bacteriology, University of Zurich Zurich, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Voegtlin
authors.affiliation: Vetsuisse Faculty, Institute for Food Safety and Hygiene, University of Zurich Zurich, Switzerland.
authors.forename: Angelika
authors.initials: A
authors.lastname: Lehner
authors.affiliation: Institute of Microbiology, University Hospital Center and University of Lausanne Lausanne, Switzerland.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Greub
authors.affiliation: Department of Molecular Medicine and Pathology, School of Medical Sciences, University of Auckland Auckland, New Zealand.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Crosier
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich Zurich, Switzerland.
authors.forename: Stephan C F
authors.initials: SC
authors.lastname: Neuhauss
authors.affiliation: Vetsuisse Faculty, Institute for Veterinary Pathology, University of Zurich Zurich, Switzerland.
authors.forename: Lloyd
authors.initials: L
authors.lastname: Vaughan
keywords: Chlamydia; MyD88; PVC superphylum; Waddlia; endothelial cells; neutrophils; swim bladder infection; zebrafish