Disruption of Toxoplasma gondii Parasitophorous Vacuoles by the Mouse p47-Resistance GTPases
| Autor: | Jens Zerrahn, Sascha Martens, Gareth Griffiths, Gaby Reichmann, Jonathan C. Howard, Iana Parvanova, Gudrun Schell |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Male
QH301-705.5 Immunology Vacuole GTPase Microbiology GTP Phosphohydrolases Host-Parasite Interactions Mice Immunity Virology parasitic diseases Genetics Parasite hosting Animals Humans Biology (General) Molecular Biology Cells Cultured biology Intracellular parasite Toxoplasma gondii Transfection Cell Biology RC581-607 biology.organism_classification Mus (mouse) Immunity Innate Cell biology In Vitro Mice Inbred C57BL Animals Newborn Astrocytes Vacuoles Cell disruption Parasitology Immunologic diseases. Allergy Toxoplasma Research Article |
| Zdroj: | PLoS Pathogens PLoS Pathogens, Vol 1, Iss 3, p e24 (2005) |
| ISSN: | 1553-7374 1553-7366 |
| Popis: | The p47 GTPases are essential for interferon-γ-induced cell-autonomous immunity against the protozoan parasite, Toxoplasma gondii, in mice, but the mechanism of resistance is poorly understood. We show that the p47 GTPases, including IIGP1, accumulate at vacuoles containing T. gondii. The accumulation is GTP-dependent and requires live parasites. Vacuolar IIGP1 accumulations undergo a maturation-like process accompanied by vesiculation of the parasitophorous vacuole membrane. This culminates in disruption of the parasitophorous vacuole and finally of the parasite itself. Over-expression of IIGP1 leads to accelerated vacuolar disruption whereas a dominant negative form of IIGP1 interferes with interferon-γ-mediated killing of intracellular parasites. Targeted deletion of the IIGP1 gene results in partial loss of the IFN-γ-mediated T. gondii growth restriction in mouse astrocytes. Synopsis Toxoplasma gondii is a small unicellular parasite infecting virtually every warm-blooded animal including humans. After infection, T. gondii does not stay in extracellular fluids such as the blood, but actively invades body cells. The parasite has developed elaborate mechanisms enabling it to form a so-called parasitophorous vacuole (PV) within the cell it invades. Within this vacuole the parasite multiplies until the host cell ruptures and the progeny are released into the extracellular space to infect further cells. Host cells have developed several special mechanisms to combat the parasite. In mice, these mechanisms include a protein family, the p47 GTPases, which are induced by immune-alert factors called interferons. This study begins to address how the mouse p47 GTPases function. The study shows that the p47 GTPases assemble on the PV very shortly after infection, apparently to form a “membrane attack complex.” Within an hour the PV membrane shows signs of damage, bulging into small out-foldings that separate from the membrane in small vesicles. Shortly afterward the PV membrane ruptures and the parasite deteriorates. The p47 GTPase have several properties in common with the dynamin GTPases, which deform cellular membranes, suggesting that the p47 GTPases function in a mechanistically similar manner. |
| Databáze: | OpenAIRE |
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