Serine/threonine protein phosphatase 1 (PP1) controls growth and reproduction in <i>Schistosoma japonicum</i>

Zhao, Lu; Lu, Zhigang; He, Xin; Mughal, Mudassar Niaz; Fang, Rui; Zhou, Yanqin; Jun, Zhao; Gasser, Robin B.; Grevelding, Christoph G.; Ye, Qing; Hu, Min

doi:10.1096/fj.201800725r

Cited by 14 publications

(8 citation statements)

References 80 publications

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“…The detection of aminopeptidase N is consistent with a previous study showing aminopeptidase activity in adult S. rodhaini [80]. Additionally, serine and threonine protein phosphatases play roles in the regulation of reproduction and growth in S. japonicum [81]. Rootletin, which was detected in this work, is expected to originate from miracidia in the ciliated larval stage [36].…”

Section: Plos Onesupporting

confidence: 92%

“…In schistosomes, protein kinase plays essential roles in growth, development, and host interaction; therefore, they have been considered as targets for drugs against parasitic diseases in many research efforts [90]. Serine/threonine protein phosphatases are important for the control of S. japonicum growth and reproduction [81], whereas cullin-3 is a core component of the E3 ubiquitin ligase complex and may play roles in the development of the reproductive organs of S. mekongi [24,91]. The 5-hydroxytryptamine receptor 1 is generally a subtype of serotonin receptor [92].…”

Section: Plos Onementioning

confidence: 99%

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Discovery of Schistosoma mekongi circulating proteins and antigens in infected mouse sera

et al. 2022

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Schistosomiasis is a neglected tropical disease caused by an infection of the parasitic flatworms schistosomes. Schistosoma mekongi is a restricted Schistosoma species found near the Mekong River, mainly in southern Laos and northern Cambodia. Because there is no vaccine or effective early diagnosis available for S. mekongi, additional biomarkers are required. In this study, serum biomarkers associated with S. mekongi-infected mice were identified at 14-, 28-, 42-, and 56-days post-infection. Circulating proteins and antigens of S. mekongi in mouse sera were analyzed using mass spectrometry-based proteomics. Serine protease inhibitors and macrophage erythroblast attacher were down-regulated in mouse sera at all infection timepoints. In addition, 54 circulating proteins and 55 antigens of S. mekongi were identified. Notable circulating proteins included kyphoscoliosis peptidase and putative tuberin, and antigens were detected at all four infection timepoints, particularly in the early stages (12 days). The putative tuberin sequence of S. mekongi was highly similar to homologs found in other members of the genus Schistosoma and less similar to human and murine sequences. Our study provided the identity of promising diagnostic biomarkers that could be applicable in early schistosomiasis diagnosis and vaccine development.

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Section: Plos Onesupporting

confidence: 92%

Section: Plos Onementioning

confidence: 99%

Discovery of Schistosoma mekongi circulating proteins and antigens in infected mouse sera

et al. 2022

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“…In eukaryotic pathogens, the important regulation roles of PP1 are getting more attentions in recent years. For instance, PP1 has been found to regulate pathogen cell maturation, proliferation, and metabolism ( 46 , 47 ). As a result, the existence of pathogen-derived PP1 within host cells may be of great importance for both pathogen cells’ intracellular proliferation and host cell manipulation.…”

Section: Discussionmentioning

confidence: 99%

E. hellemSer/Thr protein phosphatase PP1 targets the DC MAPK pathway and impairs immune functions

Bao,

Tang,

Chen

et al. 2024

Life Sci. Alliance

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Microsporidia are difficult to be completely eliminated once infected, and the persistence disrupts host cell functions. Here in this study, we aimed to elucidate the impairing effects and consequences of microsporidia on host DCs.Enterocytozoon hellem, one of the most commonly diagnosed zoonotic microsporidia species, was applied. In vivo models demonstrated thatE. hellem-infected mice were more susceptible to further pathogenic challenges, and DCs were identified as the most affected groups of cells. In vitro assays revealed thatE. helleminfection impaired DCs’ immune functions, reflected by down-regulated cytokine expressions, lower extent of maturation, phagocytosis ability, and antigen presentations.E. helleminfection also detained DCs’ potencies to prime and stimulate T cells; therefore, host immunities were disrupted. We found thatE. hellemSer/Thr protein phosphatase PP1 directly interacts with host p38α (MAPK14) to manipulate the p38α(MAPK14)/NFAT5 axis of the MAPK pathway. Our study is the first to elucidate the molecular mechanisms of the impairing effects of microsporidia on host DCs’ immune functions. The emergence of microsporidiosis may be of great threat to public health.

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“…In eukaryotic pathogens, the important regulation roles of PP1 are attracting more attention in recent years. For instance, PP1 has been found to regulate pathogen cell maturation, proliferation and metabolism (49, 50). As a result, the existence of pathogen-derived PP1 within host cells may be of great importance for both the intracellular proliferation of the pathogen as well as host cell manipulation.…”

Section: Discussionmentioning

confidence: 99%

Microsporidia Ser/Thr Protein Phosphatase PP1 Targets DCs MAPK Pathway and Impairs Immune Functions

Bao,

Tang,

Chen

et al. 2023

Preprint

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Microsporidia are difficult to be completely eliminated once infected,and the persistence may disrupt host cell functions. Here in this study, we aimed to elucidate the impairing effects and consequences of microsporidia on host dendritic cells. Enterocytozoon hellem, one of the most commonly diagnosed human-infecting microsporidia species was applied. In vivo models demonstrated that E. hellem infected mice were more susceptible to further pathogenic challenges, and DCs were identified as the most affect groups of cells. In vitro assays revealed that E. hellem infection impaired DCs immune functions as reflected by down-regulated cytokines expressions, lower extent of maturation and antigen presentations. E. hellem infection detained DCs' potencies to prime and stimulate T cells, therefore host immunities were disrupted. We further demonstrated that E. hellem Ser/Thr protein phosphatase PP1 directly interact with host p38a(MAPK14) to manipulate p38a(MAPK14)/NFAT-5 axis of the MAPK pathway. Our study is the first to elucidate the molecular mechanisms of the impairing effects of microsporidia on host DCs immune functions. The emerging of microsporidiosis may be great threat to public health.

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Serine/threonine protein phosphatase 1 (PP1) controls growth and reproduction in Schistosoma japonicum

Cited by 14 publications

References 80 publications

Discovery of Schistosoma mekongi circulating proteins and antigens in infected mouse sera

Discovery of Schistosoma mekongi circulating proteins and antigens in infected mouse sera

E. hellemSer/Thr protein phosphatase PP1 targets the DC MAPK pathway and impairs immune functions

Microsporidia Ser/Thr Protein Phosphatase PP1 Targets DCs MAPK Pathway and Impairs Immune Functions

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