Abstract
Author SummaryMany pathogens manipulate the immune system of their hosts to facilitate infection and ensure transmission to subsequent hosts. The intracellular protozoan Toxoplasma gondii, a relative of the malaria parasite, is able to infect and persist in a remarkable variety of warm-blooded hosts. Indeed roughly a third of the human race carry live Toxoplasma cysts in their brains with no overt effects. Toxoplasma infection is kept at bay in many mammals (but not in humans) by a resistance system based on a family of proteins known as the immunity-related GTPase (IRG) family. IRG proteins accumulate in infected cells on the vacuoles containing the parasite and ultimately destroy them. In this paper, we show that, in the mouse, Toxoplasma can oppose the IRG system by secreting an enzyme called ROP18 into infected cells, which phosphorylates key amino acids on the IRG proteins, rendering them inactive. Not all strains of Toxoplasma can produce an active form of ROP18, but those strains that do are more virulent. We propose that individual hosts control Toxoplasma with differing efficiency, and the variation we see in ROP18 kinase activity produced by different Toxoplasma strains is an evolutionary response to this. Thus, in different mammalian hosts, each strain seeks a balance between an excess of virulence (resulting in premature death of the host) and resistance that is too efficient (resulting in clearance of the parasite and sterile immunity).
Highlights
Toxoplasma gondii is an intracellular protozoan parasite with a complex life cycle and is distantly related to the malarial genus Plasmodium
Toxoplasma infection is kept at bay in many mammals by a resistance system based on a family of proteins known as the immunity-related GTPase (IRG) family
We show that, in the mouse, Toxoplasma can oppose the IRG system by secreting an enzyme called ROP18 into infected cells, which phosphorylates key amino acids on the IRG proteins, rendering them inactive
Summary
T. gondii establishes a lifelong chronic infection in intermediate hosts by encysting, after an initial phase of rapid intracellular proliferation and cell–cell spread, in brain and muscle. Some T. gondii strains are highly virulent for mice, killing the host as early as ten days after initial infection. In a genetic cross between a type I virulent and a type III avirulent strain, the serine-threonine kinase secreted from rhoptry organelles, ROP18 [5], emerged as a major virulence factor [6]. Comparative studies of ROP18 from multiple T. gondii strains, including the major Eurasian types, established that this virulence protein shows extensive polymorphic sequence variation derived from recent episodes of positive selection [8]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
