Infect Immun. 2014 Apr 7. [Epub ahead of print]
GRA25 is a novel virulence factor of Toxoplasma gondii and influences the host immune response
The obligate intracellular parasite Toxoplasma gondii is able to infect a broad range of hosts and cell types due, in part, to the diverse arsenal of effectors it secretes into the host cell. Here, using genetic crosses between Type II and Type III Toxoplasma strains and QTL mapping of the changes they induce in macrophage gene expression, we identify a novel dense granule protein, GRA25. Encoded on chromosome IX, GRA25 is a phosphoprotein that is secreted outside of the parasites and is found within the parasitophorous vacuole. In vitro experiments with a Type II Δgra25 strain showed that macrophages infected with this strain secrete lower levels of CCL2 and CXCL1 compared to those infected with the wild type or complemented control parasites. In vivo experiments showed that mice infected with a Type II Δgra25 strain are able to survive an otherwise lethal dose of Toxoplasma tachyzoites, and complementation of the mutant with an ectopic copy of GRA25 largely rescues this phenotype. Interestingly, the Type II and Type III versions of GRA25 vary in endogenous expression; however, both are able to promote parasite expansion in vivo when expressed in a Type II Δgra25 strain. These data establish GRA25 as a novel virulence factor and immune modulator.
- [PubMed - as supplied by publisher]