Targeted disruption of CK1α in Toxoplasma gondii increases acute virulence in mice.
Toxoplasma gondii, the causative agent of toxoplasmosis, encodes two casein kinase 1 (CK1) isoforms, CK1α and CK1β, with only CK1α having enzyme activity. Here we investigated the biological role of CK1α by construction of a CK1α deletion mutant (Δck1α) based on the type I parasite, and complement the mutant with restored expression of CK1α. Deletion of CK1α resulted in markedly defective parasite replication in vitro. Infected mice with Δck1α parasite caused suppression of IL-12 production, severe liver damage, higher tissue burdens, and short survival time relative to the CK1α-positive parental strain. Western blot analysis revealed that deletion of CK1α led to increased activation of the signal transducer and activator of transcription (STAT)-3 in infected mice and bone marrow-derived microphages. The transcriptome analysis showed that deletion of CK1α may increase expression of rhoptry proteins (ROPs). Western blot showed enhanced expression of ROP16 in the Δck1α parasite as compared with the wild-type and complemented parasites. These findings demonstrated that deletion of CK1α may increase acute virulence of T. gondii in mice by increased expression of ROPs, activation of STAT3, and suppression of IL-12 production, which have important implications for elucidating regulation mechanism of virulence factors for T. gondii.
['Wang|Zedong|Z|', 'Wang|Shuchao|S|', 'Wang|Wei|W|', 'Gu|Yi|Y|', 'Liu|Huanhuan|H|', 'Wei|Feng|F|', 'Liu|Quan|Q|']
D000818:Animals D047389:Casein Kinase I D002460:Cell Line D002478:Cells, Cultured D002522:Chlorocebus aethiops D005260:Female D005786:Gene Expression Regulation D006801:Humans D018664:Interleukin-12 D008099:Liver D051379:Mice D008807:Mice, Inbred BALB C D015800:Protozoan Proteins D050796:STAT3 Transcription Factor D016019:Survival Analysis D014122:Toxoplasma D014123:Toxoplasmosis D059467:Transcriptome D014709:Vero Cells D014774:Virulence
CK1α Toxoplasma gondii Virulence Mice IL-12 ROP16