title: Matrix metalloproteinase-9 plays a role in protecting zebrafish from lethal infection with Listeria monocytogenes by enhancing macrophage migration.
abstract: Zebrafish could serve as an alternative animal model for pathogenic bacteria in multiple infectious routes. Our previous study showed that immersion infection in zebrafish with Listeria monocytogenes did not cause lethality but induced transient expression of several immune response genes. We used an Affymetrix gene chip to examine the expression profiles of genes of zebrafish immersion-infected with L. monocytogenes. A total of 239 genes were up-regulated and 56 genes down-regulated compared with uninfected fish. Highest expression (>20-fold) was seen with the mmp-9 gene encoding the matrix metalloproteinase-9 (Mmp-9) known to degrade the extracellular matrix proteins. By morpholino knockdown of mmp-9, we found that the morphants showed rapid death with much higher bacterial load after intravenous or intraventricular (brain ventricle) infection with L. monocytogenes. Macrophages in mmp-9-knockdown morphants had significant defect in migrating to the brain cavity upon intraventricular infection. Decreased migration of murine macrophages with knockdown of mmp-9 and cd44 was also seen in transwell inserts with 8-μm pore polycarbonate membrane, as compared with the scrambled RNA. These findings suggest that Mmp-9 is a protective molecule against infection by L. monocytogenes by engaging in migration of zebrafish macrophages to the site of infection via a non-proteolytic role. Further work is required on the molecular mechanisms governing Mmp-9-driven macrophage migration in zebrafish.
authors.affiliation: Institute of Preventive Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, CHINA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shan
authors.affiliation: Institute of Preventive Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, CHINA.
authors.forename: Yikai
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Preventive Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, CHINA.
authors.forename: Xunhui
authors.initials: X
authors.lastname: Zhuo
authors.affiliation: Institute of Preventive Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, CHINA.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Preventive Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, CHINA.
authors.forename: Jinrong
authors.initials: J
authors.lastname: Peng
authors.affiliation: Institute of Preventive Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, CHINA. Electronic address: whfang@zju.edu.cn.
authors.forename: Weihuan
authors.initials: W
authors.lastname: Fang
mesh_terms: D000818:Animals; D005393:Fish Diseases / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D020869:Gene Expression Profiling; D008089:Listeria monocytogenes / Q000502:physiology*; D008088:Listeriosis / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000662:veterinary*; D008136:Longevity; D008264:Macrophages / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D029961:Zebrafish Proteins; D020780:Matrix Metalloproteinase 9
keywords: Germ-free zebrafish; Listeria monocytogenes; Macrophage; Matrix metalloproteinase-9; Microarray; Migration