title: Entrapment of intracytosolic bacteria by septin cage-like structures.
abstract: Actin-based motility is used by various pathogens for dissemination within and between cells. Yet host factors restricting this process have not been identified. Septins are GTP-binding proteins that assemble as filaments and are essential for cell division. However, their role during interphase has remained elusive. Here, we report that septin assemblies are recruited to different bacteria that polymerize actin. We observed that intracytosolic Shigella either become compartmentalized in septin cage-like structures or form actin tails. Inactivation of septin caging increases the number of Shigella with actin tails and enhances cell-to-cell spread. TNF-α, a host cytokine produced upon Shigella infection, stimulates septin caging and restricts actin tail formation and cell-to-cell spread. Finally, we show that septin cages entrap bacteria targeted to autophagy. Together, these results reveal an unsuspected mechanism of host defense that restricts dissemination of invasive pathogens.
authors.affiliation: Unité des Interactions Bactéries-Cellules, Institut Pasteur, Paris F-75015, France. smostowy@pasteur.fr
authors.forename: Serge
authors.initials: S
authors.lastname: Mostowy
authors.forename: Matteo
authors.initials: M
authors.lastname: Bonazzi
authors.forename: Mélanie Anne
authors.initials: MA
authors.lastname: Hamon
authors.forename: To Nam
authors.initials: TN
authors.lastname: Tham
authors.forename: Adeline
authors.initials: A
authors.lastname: Mallet
authors.forename: Mickaël
authors.initials: M
authors.lastname: Lelek
authors.forename: Edith
authors.initials: E
authors.lastname: Gouin
authors.forename: Caroline
authors.initials: C
authors.lastname: Demangel
authors.forename: Roland
authors.initials: R
authors.lastname: Brosch
authors.forename: Christophe
authors.initials: C
authors.lastname: Zimmer
authors.forename: Anna
authors.initials: A
authors.lastname: Sartori
authors.forename: Makoto
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Marc
authors.initials: M
authors.lastname: Lecuit
authors.forename: Pascale
authors.initials: P
authors.lastname: Cossart
mesh_terms: D000199:Actins / Q000378:metabolism; D018938:Caco-2 Cells / Q000276:immunology / Q000382:microbiology / Q000648:ultrastructure; D002584:Cervix Uteri / Q000166:cytology / Q000382:microbiology*; D003106:Colon / Q000166:cytology / Q000382:microbiology*; D003600:Cytosol / Q000382:microbiology*; D005260:Female; D006367:HeLa Cells / Q000276:immunology / Q000382:microbiology / Q000648:ultrastructure; D054884:Host-Pathogen Interactions; D006801:Humans; D058112:Septins / Q000378:metabolism*; D012763:Shigella flexneri / Q000378:metabolism / Q000472:pathogenicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000199:Actins; D014409:Tumor Necrosis Factor-alpha; D058112:Septins