title: MyD88-dependent pathway is essential for the innate immunity to Enterocytozoon bieneusi.
abstract: Enterocytozoon bieneusi is clinically the most significant microsporidian parasite associated with persistent diarrhoea, wasting and cholangitis in 30-50% of individuals with HIV/AIDS, as well as in malnutritional children and in the recipients of immunosuppressive therapy. However, the host immune responses to E. bieneusi have not been investigated until recently because of lack of sources of spores, cell culture system and animal models. In this study, we purified spores from heavily infected human or monkey faeces by serial salt-Percoll-sucrose-iodixanol centrifugation, and the purity of spores was confirmed by FACS and scanning electron microscopy. Exposure of dendritic cells to E. bieneusi spores induced the upregulation of the surface markers and production of pro-inflammatory cytokines. The cytokine production was independent of toll-like receptor 4, but MyD88 dependent, because dendritic cells from MyD88 knockout mice failed to secrete these pro-inflammatory cytokines, whereas dendritic cells from C3H/HeJ (a toll-like receptor 4 mutant) were activated by E. bieneusi and secreted these cytokines. Furthermore, MyD88-deficient mice were susceptible to E. bieneusi infection, in contrast to wild-type mice that resisted the infection. Collectively, the data demonstrate innate recognition of E. bieneusi by dendritic cells and the importance of MyD88-dependent signalling in resisting infection in a murine challenge model.
authors.affiliation: Division of Infectious Diseases, Department of Biomedical Sciences, Tufts University Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Feng
authors.forename: W
authors.initials: W
authors.lastname: Nie
authors.forename: D T
authors.initials: DT
authors.lastname: Golenbock
authors.forename: H
authors.initials: H
authors.lastname: Mayanja-Kizza
authors.forename: S
authors.initials: S
authors.lastname: Tzipori
authors.forename: H
authors.initials: H
authors.lastname: Feng
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology; D004195:Disease Models, Animal; D021862:Enterocytozoon / Q000276:immunology* / Q000302:isolation & purification; D005243:Feces / Q000382:microbiology; D000882:Haplorhini; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D016881:Microsporidiosis / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; D053594:Myeloid Differentiation Factor 88