Date:december 28, 2013

40. Transcriptional analysis of murine macrophages infected with different Toxoplasma strains identifies novel regulation of host signaling pathways.

Melo MB, Nguyen QP, Cordeiro C, Hassan MA, Yang N*, McKell R*, Rosowski EE*, Julien L, Butty V, Darde M-L, Ajzenberg D, Fitzgerald K. Young LH, Saeij JP. PLoS Pathogens. 9(12):e1003779; 2013. PDF.
Although Toxoplasma normally causes a lifelong asymtomatic infection cases of severe disease in otherwise healthy individuals have been observed. These cases are usually a result of infection with less common atypical strains. Factors associated with virulence in the atypical strains are not well understood. Here, we infected murine macrophages with 29 different Toxoplasma strains, and performed high-throughput RNA sequencing of both host cells and parasites. We found significant differences in gene expression profiles between strains. Host cell transcriptional response also varied substantially depending on the infecting strain. Specifically, we found that a small group of atypical strains are able to induce production of type I interferons, which are immunomodulatory cytokines. Interferon production is a result of the elimination of internalized parasites through a novel killing mechanism. The dataset we generated is a valuable tool for identification of host cell targets of Toxoplasma secreted effectors and can contribute to our understanding of why certain Toxoplasma strains are more prone to cause severe disease in humans.