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 DCs9 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.

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