Intrinsic toToxoplasma gondiiinfection is the parasite-induced modulation of the host immune response, which ensures establishment of a chronic lifelong infection. This manipulation of the host immune response allowsT. gondiito not only dampen the ability of the host to eliminate the parasite but also trigger parasite differentiation to the slow-growing, encysted bradyzoite form. We previously used RNA sequencing (RNA-seq) to profile the transcriptomes of mice andT. gondiiduring acute and chronic stages of infection. One of the most abundant host transcripts during acute and chronic infection was Z-DNA binding protein 1 (ZBP1). In this study, we determined that ZBP1 functions to controlT. gondiigrowth. In activated macrophages isolated from ZBP1 deletion (ZBP1−/−) mice,T. gondiihas an increased rate of replication and a decreased rate of degradation. We also identified a novel function for ZBP1 as a regulator of nitric oxide (NO) production in activated macrophages, even in the absence ofT. gondiiinfection. Upon stimulation,T. gondii-infected ZBP1−/−macrophages display increased proinflammatory cytokines compared to wild-type macrophages under the same conditions. Thesein vitrophenotypes were recapitulatedin vivo, with ZBP1−/−mice having increased susceptibility to oral challenge, higher cyst burdens during chronic infection, and elevated inflammatory cytokine responses. Taken together, these results highlight a role for ZBP1 in assisting host control ofT. gondiiinfection.
Zuotin, a putative Z-DNA binding protein in Saccharomyces cerevisiae.
