Frontiers in Immunology (Jun 2022)
Toxoplasma gondii CDPK3 Controls the Intracellular Proliferation of Parasites in Macrophages
- Minmin Wu,
- Minmin Wu,
- Minmin Wu,
- Minmin Wu,
- Ran An,
- Ran An,
- Ran An,
- Ran An,
- Nan Zhou,
- Nan Zhou,
- Nan Zhou,
- Nan Zhou,
- Ying Chen,
- Ying Chen,
- Ying Chen,
- Ying Chen,
- Haijian Cai,
- Haijian Cai,
- Qi Yan,
- Qi Yan,
- Qi Yan,
- Qi Yan,
- Ru Wang,
- Ru Wang,
- Ru Wang,
- Ru Wang,
- Qingli Luo,
- Qingli Luo,
- Li Yu,
- Li Yu,
- Li Yu,
- Lijian Chen,
- Jian Du,
- Jian Du,
- Jian Du,
- Jian Du
Affiliations
- Minmin Wu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China
- Minmin Wu
- The Research Center for Infectious Diseases, School of Basic Medical Sciences, Anhui Medical University, Hefei, China
- Minmin Wu
- The Provincial Key Laboratory of Zoonoses of High Institutions of Anhui, Anhui Medical University, Hefei, China
- Minmin Wu
- The Key Laboratory of Microbiology and Parasitology of Anhui Province, Anhui Medical University, Hefei, China
- Ran An
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China
- Ran An
- The Research Center for Infectious Diseases, School of Basic Medical Sciences, Anhui Medical University, Hefei, China
- Ran An
- The Provincial Key Laboratory of Zoonoses of High Institutions of Anhui, Anhui Medical University, Hefei, China
- Ran An
- The Key Laboratory of Microbiology and Parasitology of Anhui Province, Anhui Medical University, Hefei, China
- Nan Zhou
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China
- Nan Zhou
- The Research Center for Infectious Diseases, School of Basic Medical Sciences, Anhui Medical University, Hefei, China
- Nan Zhou
- The Provincial Key Laboratory of Zoonoses of High Institutions of Anhui, Anhui Medical University, Hefei, China
- Nan Zhou
- The Key Laboratory of Microbiology and Parasitology of Anhui Province, Anhui Medical University, Hefei, China
- Ying Chen
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China
- Ying Chen
- The Research Center for Infectious Diseases, School of Basic Medical Sciences, Anhui Medical University, Hefei, China
- Ying Chen
- The Provincial Key Laboratory of Zoonoses of High Institutions of Anhui, Anhui Medical University, Hefei, China
- Ying Chen
- School of Nursing, Anhui Medical University, Hefei, China
- Haijian Cai
- The Research Center for Infectious Diseases, School of Basic Medical Sciences, Anhui Medical University, Hefei, China
- Haijian Cai
- The Provincial Key Laboratory of Zoonoses of High Institutions of Anhui, Anhui Medical University, Hefei, China
- Qi Yan
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China
- Qi Yan
- The Research Center for Infectious Diseases, School of Basic Medical Sciences, Anhui Medical University, Hefei, China
- Qi Yan
- The Provincial Key Laboratory of Zoonoses of High Institutions of Anhui, Anhui Medical University, Hefei, China
- Qi Yan
- The Key Laboratory of Microbiology and Parasitology of Anhui Province, Anhui Medical University, Hefei, China
- Ru Wang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China
- Ru Wang
- The Research Center for Infectious Diseases, School of Basic Medical Sciences, Anhui Medical University, Hefei, China
- Ru Wang
- The Provincial Key Laboratory of Zoonoses of High Institutions of Anhui, Anhui Medical University, Hefei, China
- Ru Wang
- The Key Laboratory of Microbiology and Parasitology of Anhui Province, Anhui Medical University, Hefei, China
- Qingli Luo
- The Provincial Key Laboratory of Zoonoses of High Institutions of Anhui, Anhui Medical University, Hefei, China
- Qingli Luo
- The Key Laboratory of Microbiology and Parasitology of Anhui Province, Anhui Medical University, Hefei, China
- Li Yu
- The Research Center for Infectious Diseases, School of Basic Medical Sciences, Anhui Medical University, Hefei, China
- Li Yu
- The Provincial Key Laboratory of Zoonoses of High Institutions of Anhui, Anhui Medical University, Hefei, China
- Li Yu
- The Key Laboratory of Microbiology and Parasitology of Anhui Province, Anhui Medical University, Hefei, China
- Lijian Chen
- Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Jian Du
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China
- Jian Du
- The Research Center for Infectious Diseases, School of Basic Medical Sciences, Anhui Medical University, Hefei, China
- Jian Du
- The Provincial Key Laboratory of Zoonoses of High Institutions of Anhui, Anhui Medical University, Hefei, China
- Jian Du
- The Key Laboratory of Microbiology and Parasitology of Anhui Province, Anhui Medical University, Hefei, China
- DOI
- https://doi.org/10.3389/fimmu.2022.905142
- Journal volume & issue
-
Vol. 13
Abstract
Interferon-γ (IFN-γ)-activated macrophages restrain the replication of intracellular parasites and disrupt the integrity of vacuolar pathogens. The growth of the less virulent type II strain of Toxoplasma gondii (such as ME49) was strongly inhibited by IFN-γ-activated murine macrophages. However, the mechanism of resistance is poorly understood. Immunity-related GTPases (IRGs) as well as guanylate-binding proteins (GBPs) contributed to this antiparasitic effect. Previous studies showed the cassette of autophagy-related proteins including Atg7, Atg3, and Atg12-Atg5-Atg16L1 complex, plays crucial roles in the proper targeting of IFN-γ effectors onto the parasitophorous vacuole (PV) membrane of Toxoplasma gondii and subsequent control of parasites. TgCDPK3 is a calcium dependent protein kinase, located on the parasite periphery, plays a crucial role in parasite egress. Herein, we show that the less virulent strain CDPK3 (ME49, type II) can enhance autophagy activation and interacts with host autophagy proteins Atg3 and Atg5. Infection with CDPK3-deficient ME49 strain resulted in decreased localization of IRGs and GBPs around PV membrane. In vitro proliferation and plaque assays showed that CDPK3-deficient ME49 strain replicated significantly more quickly than wild-type parasites. These data suggested that TgCDPK3 interacts with the host Atg3 and Atg5 to promote the localization of IRGs and GBPs around PV membrane and inhibits the intracellular proliferation of parasites, which is beneficial to the less virulent strain of Toxoplasma gondii long-term latency in host cells.
Keywords
