A Novel wx2 Gene of Toxoplasma gondii Inhibits the Parasitic Invasion and Proliferation in vitro and Attenuates Virulence in vivo via Immune Response Modulation
| Autor: | Jie Guan, Jie Zhang, Yehong Huang, Kang Yan, Ruo-Lan Jiang, Xiang Wu, Linfei Yang, Yunfeng Chang, Zhenrong Ma, Bin Lu, Xuanwu Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Microbiology (medical)
CRISPR-Cas9 system Cellular immunity gene functions Mutant lcsh:QR1-502 virulence factors Virulence Toxoplasma gondii Biology Microbiology lcsh:Microbiology immune response gene knockout 03 medical and health sciences Immune system Immunity parasitic diseases medicine Interferon gamma Gene knockout 030304 developmental biology Original Research 0303 health sciences wx2 gene 030306 microbiology Correction biology.organism_classification medicine.drug |
| Zdroj: | Frontiers in Microbiology Frontiers in Microbiology, Vol 11 (2020) |
| ISSN: | 1664-302X |
| Popis: | Toxoplasma gondii (T. gondii) is an obligate intracellular apicomplexan protozoan that can parasitize most warm-blooded animals and cause severe diseases in immunocompromised individuals or fetal abnormalities in pregnant woman. The treatment of toxoplamosis has been limited by effective drugs. Our previous work indicated that the novel gene wx2 of T. gondii may serve as a vaccine antigen candidate. To further investigate the molecular functions of wx2 in highly virulent T. gondii (RH strain), a wx2 gene deletion mutant RH strain (KO-wx2) was established using CRISPR-Cas9. The phynotype of KO-wx2 was analyzed by plaque, invasion, and replication assays in vitro as well as in vivo virulence assays. The results indicated that the targeted deletion of the wx2 gene significantly inhibited in vitro parasite growth and replication in the host cells as well as attenuated parasite virulence in the mouse model. Notably, the percentage of pro-inflammatory factors of interferon gamma (IFN-γ) and interlukin-17A (IL-17A) and anti-inflammatory factor of interlukin-10 (IL-10) in the lymph nodes were upregulated in mice infected with the KO-wx2 strain. Our data suggested that the wx2 gene plays an important role in the process of the parasite's life cycle and virulence in mice. In addition, it also plays an important role in the host's immunity reaction, mainly via Th1 and Th17 cellular immunity, not Th2. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|