title: AMA1-deficient Toxoplasma gondii parasites transiently colonize mice and trigger an innate immune response that leads to long-lasting protective immunity.
abstract: The apical membrane antigen 1 (AMA1) protein was believed to be essential for the perpetuation of two Apicomplexa parasite genera, Plasmodium and Toxoplasma, until we genetically engineered viable parasites lacking AMA1. The reduction in invasiveness of the Toxoplasma gondii RH-AMA1 knockout (RH-AMA1(KO)) tachyzoite population, in vitro, raised key questions about the outcome associated with these tachyzoites once inoculated in the peritoneal cavity of mice. In this study, we used AMNIS technology to simultaneously quantify and image the parasitic process driven by AMA1(KO) tachyzoites. We report their ability to colonize and multiply in mesothelial cells and in both resident and recruited leukocytes. While the RH-AMA1(KO) population amplification is rapidly lethal in immunocompromised mice, it is controlled in immunocompetent hosts, where immune cells in combination sense parasites and secrete proinflammatory cytokines. This innate response further leads to a long-lasting status immunoprotective against a secondary challenge by high inocula of the homologous type I or a distinct type II T. gondii genotypes. While AMA1 is definitively not an essential protein for tachyzoite entry and multiplication in host cells, it clearly assists the expansion of parasite population in vivo.
authors.affiliation: INSERM U1016, Institut Cochin, Paris, France CNRS UMR8104, Paris, France Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Lagal
authors.affiliation: INSERM U1016, Institut Cochin, Paris, France CNRS UMR8104, Paris, France Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Márcia
authors.initials: M
authors.lastname: Dinis
authors.affiliation: CNRS UMR5163, LAPM, Grenoble, France Université Joseph Fourier, Grenoble, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Cannella
authors.affiliation: Institut Pasteur, Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bargieri
authors.affiliation: INSERM U1016, Institut Cochin, Paris, France CNRS UMR8104, Paris, France Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Gonzalez
authors.affiliation: Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity Inflammation, College of Medical, Veterinary and Life Sciences, Glasgow, Lanarkshire, United Kingdom.
authors.forename: Nicole
authors.initials: N
authors.lastname: Andenmatten
authors.affiliation: Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity Inflammation, College of Medical, Veterinary and Life Sciences, Glasgow, Lanarkshire, United Kingdom.
authors.forename: Markus
authors.initials: M
authors.lastname: Meissner
authors.affiliation: INSERM U1016, Institut Cochin, Paris, France CNRS UMR8104, Paris, France Université Paris Descartes, Sorbonne Paris Cité, Paris, France isabelle.tardieux@inserm.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Tardieux
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005796:Genes; D007113:Immunity, Innate / Q000502:physiology*; D016867:Immunocompromised Host; D017737:Macrophages, Peritoneal; D051379:Mice; D008815:Mice, Inbred Strains; D016052:Protozoan Vaccines / Q000276:immunology*; D014122:Toxoplasma / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology*; D014124:Toxoplasmosis, Animal / Q000517:prevention & control*; D014613:Vaccines, Attenuated; D014774:Virulence
chemical_list: C506564:AMA1 protein, Toxoplasma gondii; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D016052:Protozoan Vaccines; D014613:Vaccines, Attenuated
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