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Methods for the Measurement of Early Events in Toxoplasma gondii Immunity in Mo...

Alvarez, Catalina; Campos, Ana Claudia; Howard, Jonathan C; Loureiro, Joana; Müller, Urs Benedikt; Rodrigues, Ana Lina

Critical steps in resistance of mice against Toxoplasma gondii occur in the first 2 or 3 h after the pathogen has entered a cell that has been exposed to interferon γ (IFNγ). The newly formed parasitophorous vacuole is attacked by the IFNγ-inducible IRG proteins and disrupted, resulting in death of the parasite and necrotic death of the cell. Here we describe some techniques that we have used to describe and qu...


Irgm2 and Gate‐16 cooperatively dampen Gram‐negative bacteria‐induced caspase‐1...

Eren, Elif; Planès, Rémi; Bagayoko, Salimata; Bordignon, Pierre‐Jean; Chaoui, Karima; Hessel, Audrey; Santoni, Karin; Pinilla, Miriam; Lagrange, Brice

Inflammatory caspase-11 (rodent) and caspases-4/5 (humans) detect the Gram-negative bacterial component LPS within the host cell cytosol, promoting activation of the non-canonical inflammasome. Although non-canonical inflammasome-induced pyroptosis and IL-1-related cytokine release are crucial to mount an efficient immune response against various bacteria, their unrestrained activation drives sepsis. This sugge...


Molecular mechanism for the control of virulent Toxoplasma gondii infections in...

Murillo-León, Mateo; Müller, Urs B; Zimmermann, Ines; Singh, Shishir; Widdershooven, Pia; Campos, Cláudia; Alvarez, Catalina; Könen-Waisman, Stephanie

Some strains of the protozoan parasite Toxoplasma gondii (such as RH) are virulent in laboratory mice because they are not restricted by the Immunity-Related GTPase (IRG) resistance system in these mouse strains. In some wild-derived Eurasian mice (such as CIM) on the other hand, polymorphic IRG proteins inhibit the replication of such virulent T. gondii strains. Here we show that this resistance is due to dire...


The impact of Toxoplasma gondii on the mammalian genome

Müller, Urs B; Howard, Jonathan C

Nobody doubts that infections have imposed specialisations on the mammalian genome. However sufficient information is usually missing to attribute a specific genomic modification to pressure from a specific pathogen. Recent studies on mechanisms of mammalian resistance against the ubiquitous protozoan parasite, Toxoplasma gondii, have shown that the small rodents presumed to be largely responsible for transmiss...


The Toxoplasma gondii rhoptry protein ROP18 is an Irga6-specific kinase and reg...

Hermanns, Thomas; Müller, Urs B; Könen-Waisman, Stephanie; Howard, Jonathan C; Steinfeldt, Tobias

In mice, avirulent strains (e.g. types II and III) of the protozoan parasite Toxoplasma gondii are restricted by the immunity-related GTPase (IRG) resistance system. Loading of IRG proteins onto the parasitophorous vacuolar membrane (PVM) is required for vacuolar rupture resulting in parasite clearance. In virulent strain (e.g. type I) infections, polymorphic effector proteins ROP5 and ROP18 cooperate to phosph...


Reciprocal virulence and resistance polymorphism in the relationship betweenTox...

Lilue, Jingtao; Müller, Urs Benedikt; Steinfeldt, Tobias; Howard, Jonathan C

Virulence in the ubiquitous intracellular protozoon Toxoplasma gondii for its natural intermediate host, the mouse, appears paradoxical from an evolutionary standpoint because death of the mouse before encystment interrupts the parasite life cycle. Virulent T. gondii strains secrete kinases and pseudokinases that inactivate the immunity-related GTPases (IRG proteins) responsible for mouse resistance to avirulen...


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