title: Apical Organelle Secretion by Toxoplasma Controls Innate and Adaptive Immunity and Mediates Long-Term Protection.
abstract: Apicomplexan parasites have unique apical rhoptry and microneme secretory organelles that are crucial for host infection, although their role in protection against Toxoplasma gondii infection is not thoroughly understood. Here, we report a novel function of the endolysosomal T. gondii sortilin-like receptor (TgSORTLR), which mediates trafficking to functional apical organelles and their subsequent secretion of virulence factors that are critical to the induction of sterile immunity against parasite reinfection. We further demonstrate that the T. gondii armadillo repeats-only protein (TgARO) mutant, which is deficient only in apical secretion of rhoptries, is also critical in mounting protective immunity. The lack of TgSORTLR and TgARO proteins completely inhibited T-helper 1-dependent adaptive immunity and compromised the function of natural killer T-cell-mediated innate immunity. Our findings reveal an essential role for apical secretion in promoting sterile protection against T. gondii and provide strong evidence for rhoptry-regulated discharge of antigens as a key effector for inducing protective immunity.
authors.affiliation: Laboratory of Cellular and Molecular Biology of Toxoplasma.
authors.forename: Pierre-Julien
authors.initials: PJ
authors.lastname: Sloves
authors.affiliation: Laboratory of Cellular and Molecular Biology of Toxoplasma.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mouveaux
authors.affiliation: Laboratory of Pulmonary Immunity, Center for Infection and Immunity of Lille, Centre National de la Recherche Scientfique (CNRS) Unité Mixte de Recherche (UMR) 8204, Institut National de la Santé et de la Recherche Médicale (NSERM), Unité ( U) 1019, Université de Lille, Institut Pasteur de Lille, France.
authors.forename: Saliha
authors.initials: S
authors.lastname: Ait-Yahia
authors.affiliation: Laboratory of Pulmonary Immunity, Center for Infection and Immunity of Lille, Centre National de la Recherche Scientfique (CNRS) Unité Mixte de Recherche (UMR) 8204, Institut National de la Santé et de la Recherche Médicale (NSERM), Unité ( U) 1019, Université de Lille, Institut Pasteur de Lille, France.
authors.forename: Han
authors.initials: H
authors.lastname: Vorng
authors.affiliation: Laboratory of Pulmonary Immunity, Center for Infection and Immunity of Lille, Centre National de la Recherche Scientfique (CNRS) Unité Mixte de Recherche (UMR) 8204, Institut National de la Santé et de la Recherche Médicale (NSERM), Unité ( U) 1019, Université de Lille, Institut Pasteur de Lille, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Everaere
authors.affiliation: Laboratory of Cellular and Molecular Biology of Toxoplasma.
authors.forename: Lamba Omar
authors.initials: LO
authors.lastname: Sangare
authors.affiliation: Laboratory of Pulmonary Immunity, Center for Infection and Immunity of Lille, Centre National de la Recherche Scientfique (CNRS) Unité Mixte de Recherche (UMR) 8204, Institut National de la Santé et de la Recherche Médicale (NSERM), Unité ( U) 1019, Université de Lille, Institut Pasteur de Lille, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Tsicopoulos
authors.affiliation: Laboratory of Cellular and Molecular Biology of Toxoplasma.
authors.forename: Stanislas
authors.initials: S
authors.lastname: Tomavo
mesh_terms: D056704:Adaptive Immunity; D033942:Adaptor Proteins, Vesicular Transport / Q000276:immunology; D000818:Animals; D000953:Antigens, Protozoan / Q000097:blood; D002460:Cell Line; D006790:Host-Parasite Interactions; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology; D015388:Organelles / Q000276:immunology*; D021381:Protein Transport / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D000953:Antigens, Protozoan; D007371:Interferon-gamma; D016753:Interleukin-10; D053583:Interleukin-1beta; D015800:Protozoan Proteins; D000099183:Sortilin
keywords: apical secretion; long-term protection; organelle biogenesis; recall immunity; rhoptry organelles