Ferreira-da-Silva, Marialice da Fonseca, Springer-Frauenhoff, Helen Maria, Bohne, Wolfgang and Howard, Jonathan C. (2014). Identification of the Microsporidian Encephalitozoon cuniculi as a New Target of the IFN gamma-Inducible IRG Resistance System. PLoS Pathog., 10 (10). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1553-7374
Full text not available from this repository.Abstract
The IRG system of IFN gamma-inducible GTPases constitutes a powerful resistance mechanism in mice against Toxoplasma gondii and two Chlamydia strains but not against many other bacteria and protozoa. Why only T. gondii and Chlamydia? We hypothesized that unusual features of the entry mechanisms and intracellular replicative niches of these two organisms, neither of which resembles a phagosome, might hint at a common principle. We examined another unicellular parasitic organism of mammals, member of an early-diverging group of Fungi, that bypasses the phagocytic mechanism when it enters the host cell: the microsporidian Encephalitozoon cuniculi. Consistent with the known susceptibility of IF4y-deficient mice to E. cunkull infection, we found that IFN gamma treatment suppresses meront development and spore formation in mouse fibroblasts in vitro, and that this effect is mediated by IRG proteins. The process resembles that previously described in T. gondii and Chlamydia resistance. Effector (GKS subfamily) IRG proteins accumulate at the parasitophorous vacuole of E. cuniculi and the meronts are eliminated. The suppression of E. cuniculi growth by IFN gamma is completely reversed in cells lacking regulatory (GMS subfamily) IRG proteins, cells that effectively lack all IRG function. In addition IFN gamma-induced cells infected with E. cuniculi die by necrosis as previously shown for IFN gamma-induced cells resisting T. gondil infection. Thus the IRG resistance system provides cell-autonomous immunity to specific parasites from three kingdoms of life: protozoa, bacteria and fungi. The phylogenetic divergence of the three organisms whose vacuoles are now known to be involved in IRGmediated immunity and the non-phagosomal character of the vacuoles themselves strongly suggests that the IRG system is triggered not by the presence of specific parasite components but rather by absence of specific host components on the vacuolar membrane.
| Item Type: | Journal Article | ||||||||||||||||||||
| Creators: |
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| URN: | urn:nbn:de:hbz:38-426447 | ||||||||||||||||||||
| DOI: | 10.1371/journal.ppat.1004449 | ||||||||||||||||||||
| Journal or Publication Title: | PLoS Pathog. | ||||||||||||||||||||
| Volume: | 10 | ||||||||||||||||||||
| Number: | 10 | ||||||||||||||||||||
| Date: | 2014 | ||||||||||||||||||||
| Publisher: | PUBLIC LIBRARY SCIENCE | ||||||||||||||||||||
| Place of Publication: | SAN FRANCISCO | ||||||||||||||||||||
| ISSN: | 1553-7374 | ||||||||||||||||||||
| Language: | English | ||||||||||||||||||||
| Faculty: | Unspecified | ||||||||||||||||||||
| Divisions: | Unspecified | ||||||||||||||||||||
| Subjects: | no entry | ||||||||||||||||||||
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| URI: | http://kups.ub.uni-koeln.de/id/eprint/42644 |
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