<i>Toxoplasma gondii</i> Rhoptry Protein 7 (ROP7) Interacts with NLRP3 and Promotes Inflammasome Hyperactivation in THP-1-Derived Macrophages
Lijun Zhu,
Wanjun Qi,
Guang Yang,
Yurong Yang,
Yuwen Wang,
Lulu Zheng,
Yongfeng Fu,
Xunjia Cheng
Affiliations
Lijun Zhu
Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
Wanjun Qi
Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
Guang Yang
Department of Pathogen Biology, School of Medicine, Jinan University, Guangzhou 510632, China
Yurong Yang
College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China
Yuwen Wang
Engineering Research Center of Optical Instrument and System, The Ministry of Education, Shanghai Key Laboratory of Modern Optical System, University of Shanghai for Science and Technology, Shanghai 200093, China
Lulu Zheng
Engineering Research Center of Optical Instrument and System, The Ministry of Education, Shanghai Key Laboratory of Modern Optical System, University of Shanghai for Science and Technology, Shanghai 200093, China
Yongfeng Fu
Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
Xunjia Cheng
Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
Toxoplasma gondii is a common opportunistic protozoan pathogen that can parasitize the karyocytes of humans and virtually all other warm-blooded animals. In the host’s innate immune response to T. gondii infection, inflammasomes can mediate the maturation of pro-IL-1β and pro-IL-18, which further enhances the immune response. However, how intercellular parasites specifically provoke inflammasome activation remains unclear. In this study, we found that the T. gondii secretory protein, rhoptry protein 7 (ROP7), could interact with the NACHT domain of NLRP3 through liquid chromatography-mass spectrometry analysis and co-immunoprecipitation assays. When expressing ROP7 in differentiated THP-1 cells, there was significant up-regulation in NF-κB and continuous release of IL-1β. This process is pyroptosis-independent and leads to inflammasome hyperactivation through the IL-1β/NF-κB/NLRP3 feedback loop. The loss of ROP7 in tachyzoites did not affect parasite proliferation in host cells but did attenuate parasite-induced inflammatory activity. In conclusion, these findings unveil that a T. gondii-derived protein is able to promote inflammasome activation, and further study of ROP7 will deepen our understanding of host innate immunity to parasites.
