Host autophagy limits Toxoplasma gondii proliferation in the absence of IFN-γ by affecting the hijack of Rab11A-positive vesicles
IntroductionAutophagy has been recognized as a bona fide immunological process. Evidence has shown that this process in IFN-γ stimulated cells controls Toxoplasma gondii proliferation or eliminates its infection. However, little is known about the effect of T. gondii infection on the host cell autop...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-12-01
|
| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2022.1052779/full |
| _version_ | 1811320523062247424 |
|---|---|
| author | Lingtao Pan Yimin Yang Xueqiu Chen Mingxiu Zhao Chaoqun Yao Kaiyin Sheng Yi Yang Guangxu Ma Aifang Du |
| author_facet | Lingtao Pan Yimin Yang Xueqiu Chen Mingxiu Zhao Chaoqun Yao Kaiyin Sheng Yi Yang Guangxu Ma Aifang Du |
| author_sort | Lingtao Pan |
| collection | DOAJ |
| description | IntroductionAutophagy has been recognized as a bona fide immunological process. Evidence has shown that this process in IFN-γ stimulated cells controls Toxoplasma gondii proliferation or eliminates its infection. However, little is known about the effect of T. gondii infection on the host cell autophagy in the absence of IFN-γ.MethodsMultiple autophagy detection methods and CRISPR/CAS9 technology were used to study T. gondii-induced autophagy in HeLa and several other mammalian cell lines.ResultsHere, we report increased LC3 II, autophagosome-like membrane structures, enhanced autophagic flux, and decreased lysosomes in a range of mammalian cell lines without IFN-γ treatment after T. gondii infection. Specifically, disruption of host atg5 (a necessary gene for autophagy) in HeLa cells promoted the intracellular replication of T. gondii, with the transcript level of rab11a increased, compared with that in wild-type cells. Further, after T. gondii infection, the abundance of Rab11A remained stable in wild-type HeLa cells but decreased in atg5−/− mutant. Disruption of rab11a in the HeLa cells compromised the proliferation of T. gondii, and increased the transcription of gra2 in the parasite. Compared to the T. gondii wild-type RH∆ku80 strain, the ∆gra2 mutant induces enhanced host autophagy in HeLa cells, and results in slower replication of the parasite.DiscussionCollectively, these results indicate that host cell autophagy can limit T. gondii proliferation in an IFN-γ independent manner, possibly by affecting the hijack of host Rab11A-positive vesicles by the parasite which involved TgGRA2. The findings provide novel insights into T. gondii infection in host cells and toxoplasmosis research. |
| first_indexed | 2024-04-13T13:01:08Z |
| format | Article |
| id | doaj.art-c5e6bbf59063498caa5b83449d699280 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-13T13:01:08Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-c5e6bbf59063498caa5b83449d6992802022-12-22T02:45:54ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-12-011310.3389/fmicb.2022.10527791052779Host autophagy limits Toxoplasma gondii proliferation in the absence of IFN-γ by affecting the hijack of Rab11A-positive vesiclesLingtao Pan0Yimin Yang1Xueqiu Chen2Mingxiu Zhao3Chaoqun Yao4Kaiyin Sheng5Yi Yang6Guangxu Ma7Aifang Du8Institute of Preventive Veterinary Medicine and Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, ChinaInstitute of Preventive Veterinary Medicine and Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, ChinaInstitute of Preventive Veterinary Medicine and Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, ChinaInstitute of Preventive Veterinary Medicine and Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, ChinaDepartment of Biomedical Sciences and One Health Center for Zoonoses and Tropical Veterinary Medicine, Ross University School of Veterinary Medicine, Basseterre, Saint Kitts and Nevis, West IndiesInstitute of Preventive Veterinary Medicine and Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, ChinaInstitute of Preventive Veterinary Medicine and Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, ChinaInstitute of Preventive Veterinary Medicine and Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, ChinaInstitute of Preventive Veterinary Medicine and Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, ChinaIntroductionAutophagy has been recognized as a bona fide immunological process. Evidence has shown that this process in IFN-γ stimulated cells controls Toxoplasma gondii proliferation or eliminates its infection. However, little is known about the effect of T. gondii infection on the host cell autophagy in the absence of IFN-γ.MethodsMultiple autophagy detection methods and CRISPR/CAS9 technology were used to study T. gondii-induced autophagy in HeLa and several other mammalian cell lines.ResultsHere, we report increased LC3 II, autophagosome-like membrane structures, enhanced autophagic flux, and decreased lysosomes in a range of mammalian cell lines without IFN-γ treatment after T. gondii infection. Specifically, disruption of host atg5 (a necessary gene for autophagy) in HeLa cells promoted the intracellular replication of T. gondii, with the transcript level of rab11a increased, compared with that in wild-type cells. Further, after T. gondii infection, the abundance of Rab11A remained stable in wild-type HeLa cells but decreased in atg5−/− mutant. Disruption of rab11a in the HeLa cells compromised the proliferation of T. gondii, and increased the transcription of gra2 in the parasite. Compared to the T. gondii wild-type RH∆ku80 strain, the ∆gra2 mutant induces enhanced host autophagy in HeLa cells, and results in slower replication of the parasite.DiscussionCollectively, these results indicate that host cell autophagy can limit T. gondii proliferation in an IFN-γ independent manner, possibly by affecting the hijack of host Rab11A-positive vesicles by the parasite which involved TgGRA2. The findings provide novel insights into T. gondii infection in host cells and toxoplasmosis research.https://www.frontiersin.org/articles/10.3389/fmicb.2022.1052779/fullautophagyToxoplasma gondiiproliferationRab11ATgGRA2 |
| spellingShingle | Lingtao Pan Yimin Yang Xueqiu Chen Mingxiu Zhao Chaoqun Yao Kaiyin Sheng Yi Yang Guangxu Ma Aifang Du Host autophagy limits Toxoplasma gondii proliferation in the absence of IFN-γ by affecting the hijack of Rab11A-positive vesicles Frontiers in Microbiology autophagy Toxoplasma gondii proliferation Rab11A TgGRA2 |
| title | Host autophagy limits Toxoplasma gondii proliferation in the absence of IFN-γ by affecting the hijack of Rab11A-positive vesicles |
| title_full | Host autophagy limits Toxoplasma gondii proliferation in the absence of IFN-γ by affecting the hijack of Rab11A-positive vesicles |
| title_fullStr | Host autophagy limits Toxoplasma gondii proliferation in the absence of IFN-γ by affecting the hijack of Rab11A-positive vesicles |
| title_full_unstemmed | Host autophagy limits Toxoplasma gondii proliferation in the absence of IFN-γ by affecting the hijack of Rab11A-positive vesicles |
| title_short | Host autophagy limits Toxoplasma gondii proliferation in the absence of IFN-γ by affecting the hijack of Rab11A-positive vesicles |
| title_sort | host autophagy limits toxoplasma gondii proliferation in the absence of ifn γ by affecting the hijack of rab11a positive vesicles |
| topic | autophagy Toxoplasma gondii proliferation Rab11A TgGRA2 |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2022.1052779/full |
| work_keys_str_mv | AT lingtaopan hostautophagylimitstoxoplasmagondiiproliferationintheabsenceofifngbyaffectingthehijackofrab11apositivevesicles AT yiminyang hostautophagylimitstoxoplasmagondiiproliferationintheabsenceofifngbyaffectingthehijackofrab11apositivevesicles AT xueqiuchen hostautophagylimitstoxoplasmagondiiproliferationintheabsenceofifngbyaffectingthehijackofrab11apositivevesicles AT mingxiuzhao hostautophagylimitstoxoplasmagondiiproliferationintheabsenceofifngbyaffectingthehijackofrab11apositivevesicles AT chaoqunyao hostautophagylimitstoxoplasmagondiiproliferationintheabsenceofifngbyaffectingthehijackofrab11apositivevesicles AT kaiyinsheng hostautophagylimitstoxoplasmagondiiproliferationintheabsenceofifngbyaffectingthehijackofrab11apositivevesicles AT yiyang hostautophagylimitstoxoplasmagondiiproliferationintheabsenceofifngbyaffectingthehijackofrab11apositivevesicles AT guangxuma hostautophagylimitstoxoplasmagondiiproliferationintheabsenceofifngbyaffectingthehijackofrab11apositivevesicles AT aifangdu hostautophagylimitstoxoplasmagondiiproliferationintheabsenceofifngbyaffectingthehijackofrab11apositivevesicles |