Identification of the Microsporidian as a New Target of the IFNγ-Inducible IRG Resistance System


For some time we have studied an intracellular resistance system essential for mice to survive infection with the intracellular protozoan, Toxoplasma gondii, that is based on a family of proteins, immunity-related GTPases or IRG proteins. Immediately after the parasite enters a cell, IRG proteins accumulate on the membrane of the vacuole in which the organism resides. Within a few hours the vacuole membrane breaks down and the parasite dies. A puzzle is why this mechanism works on Toxoplasma, but only on one other organism among the many tested, namely the bacterial species, Chlamydia. What do these widely different parasites have in common that so many other bacteria and protozoa lack? Neither Toxoplasma nor Chlamydia is taken up by conventional phagocytosis. In this paper we suggest that this is an important clue by showing that a microsporidian, Encephalitozoon cuniculi, a highly-divergent fungal parasite, which also invades cells bypassing phagocytosis, is resisted by the IRG system. Therefore, we propose here the “missing self” principle: IRG proteins bind to vacuolar membranes only in the absence of a host derived inhibitor that is present on phagosomal membranes but excluded from the plasma membrane invaginated by IRG target organisms during non-phagosomal entry.


Vyšlo v časopise: Identification of the Microsporidian as a New Target of the IFNγ-Inducible IRG Resistance System. PLoS Pathog 10(10): e32767. doi:10.1371/journal.ppat.1004449
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004449

Souhrn

For some time we have studied an intracellular resistance system essential for mice to survive infection with the intracellular protozoan, Toxoplasma gondii, that is based on a family of proteins, immunity-related GTPases or IRG proteins. Immediately after the parasite enters a cell, IRG proteins accumulate on the membrane of the vacuole in which the organism resides. Within a few hours the vacuole membrane breaks down and the parasite dies. A puzzle is why this mechanism works on Toxoplasma, but only on one other organism among the many tested, namely the bacterial species, Chlamydia. What do these widely different parasites have in common that so many other bacteria and protozoa lack? Neither Toxoplasma nor Chlamydia is taken up by conventional phagocytosis. In this paper we suggest that this is an important clue by showing that a microsporidian, Encephalitozoon cuniculi, a highly-divergent fungal parasite, which also invades cells bypassing phagocytosis, is resisted by the IRG system. Therefore, we propose here the “missing self” principle: IRG proteins bind to vacuolar membranes only in the absence of a host derived inhibitor that is present on phagosomal membranes but excluded from the plasma membrane invaginated by IRG target organisms during non-phagosomal entry.


Zdroje

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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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