E. hellem Ser/Thr protein phosphatase PP1 targets the DC MAPK pathway and impairs immune functions.
Life Sci Alliance
; 7(4)2024 Apr.
Article
em En
| MEDLINE
| ID: mdl-38199846
ABSTRACT
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 that E. 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 that E. hellem infection impaired DCs' immune functions, reflected by down-regulated cytokine expressions, lower extent of maturation, phagocytosis ability, and antigen presentations. E. hellem infection also detained DCs' potencies to prime and stimulate T cells; therefore, host immunities were disrupted. We found that E. hellem Ser/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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteína Quinase 14 Ativada por Mitógeno
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article