title: Toxoplasma gondii-infected natural killer cells display a hypermotility phenotype in vivo.
abstract: Toxoplasma gondii is a highly prevalent intracellular protozoan parasite that causes severe disease in congenitally infected or immunocompromised hosts. T. gondii is capable of invading immune cells and it has been suggested that the parasite harnesses the migratory pathways of these cells to spread through the body. Although in vitro evidence suggests that the parasite further enhances its spread by inducing a hypermotility phenotype in parasitized immune cells, in vivo evidence for this phenomenon is scarce. Here we use a physiologically relevant oral model of T. gondii infection, in conjunction with two-photon laser scanning microscopy, to address this issue. We found that a small proportion of natural killer (NK) cells in mesenteric lymph nodes contained parasites. Compared with uninfected 'bystander' NK cells, these infected NK cells showed faster, more directed and more persistent migratory behavior. Consistent with this, infected NK cells showed impaired spreading and clustering of the integrin, LFA-1, when exposed to plated ligands. Our results provide the first evidence for a hypermigratory phenotype in T. gondii-infected NK cells in vivo, providing an anatomical context for understanding how the parasite manipulates immune cell motility to spread through the host.
authors.affiliation: Department of Molecular Biology and Biochemistry and The Institute for Immunology, University of California, Irvine, CA, USA.
authors.forename: Norikiyo
authors.initials: N
authors.lastname: Ueno
authors.affiliation: Department of Molecular Biology and Biochemistry and The Institute for Immunology, University of California, Irvine, CA, USA.
authors.forename: Melissa B
authors.initials: MB
authors.lastname: Lodoen
authors.affiliation: Department of Epidemiology and Population Health, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
authors.forename: Graeme L
authors.initials: GL
authors.lastname: Hickey
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Robey
authors.affiliation: Department of Infection Biology, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
authors.forename: Janine L
authors.initials: JL
authors.lastname: Coombes
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002465:Cell Movement; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000469:parasitology; D008198:Lymph Nodes / Q000473:pathology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D023421:Models, Animal; D010641:Phenotype; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology* / Q000635:transmission
chemical_list: D016169:Lymphocyte Function-Associated Antigen-1