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MyD88‐dependent pathway is essential for the innate immunity to Enterocytozoon bieneusi
Author(s) -
ZHANG Q.,
FENG X.,
NIE W.,
GOLENBOCK D. T.,
MAYANJAKIZZA H.,
TZIPORI S.,
FENG H.
Publication year - 2011
Publication title -
parasite immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 75
eISSN - 1365-3024
pISSN - 0141-9838
DOI - 10.1111/j.1365-3024.2010.01269.x
Subject(s) - enterocytozoon bieneusi , biology , innate immune system , immunology , immunity , virology , microsporidiosis , immune system , malaria , protozoal disease
Summary 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.