Head-to-head comparisons of Toxoplasma gondii and its near relative Hammondia hammondi reveal dramatic differences in the host response and effectors with species-specific functions.
Toxoplasma gondii and Hammondia hammondi are closely-related coccidian intracellular parasites that differ in their ability to cause disease in animal and (likely) humans. The role of the host response in these phenotypic differences is not known and to address this we performed a transcriptomic ana...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-06-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1008528 |
| Summary: | Toxoplasma gondii and Hammondia hammondi are closely-related coccidian intracellular parasites that differ in their ability to cause disease in animal and (likely) humans. The role of the host response in these phenotypic differences is not known and to address this we performed a transcriptomic analysis of a monocyte cell line (THP-1) infected with these two parasite species. The pathways altered by infection were shared between species ~95% the time, but the magnitude of the host response to H. hammondi was significantly higher compared to T. gondii. Accompanying this divergent host response was an equally divergent impact on the cell cycle of the host cell. In contrast to T. gondii, H. hammondi infection induces cell cycle arrest via pathways linked to DNA-damage responses and cellular senescence and robust secretion of multiple chemokines that are known to be a part of the senescence associated secretory phenotype (SASP). Remarkably, prior T. gondii infection or treatment with T. gondii-conditioned media suppressed responses to H. hammondi infection, and promoted the replication of H. hammondi in recipient cells. Suppression of inflammatory responses to H. hammondi was found to be mediated by the T. gondii effector IST, and this finding was consistent with reduced functionality of the H. hammondi IST ortholog compared to its T. gondii counterpart. Taken together our data suggest that T. gondii manipulation of the host cell is capable of suppressing previously unknown stress and/or DNA-damage induced responses that occur during infection with H. hammondi, and that one important impact of this T. gondii mediated suppression is to promote parasite replication. |
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| ISSN: | 1553-7366 1553-7374 |