Toxoplasma gondii mitogen-activated protein kinases are associated with inflammasome activation in infected mice
Shuchao Wang1, Zedong Wang1, Yi Gu1
1Military Veterinary Institute, Academy of Military Medical Sciences, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, 666 Liuying West Road, Changchun 130122, Jilin Province, China.
Abstract:
Toxoplasma gondii can activate the nucleotide-binding domain and leucine-rich repeat-containing proteins NLRP1/3 inflammasomes, which mediate host resistance to the infection. Here we showed that deletion of mitogen-activated protein kinases MAPK1 and MAPK2 of type I parasite decreases acute virulence in mice, characterized by low levels of interleukin (IL)-18, NLRP1/3, ASC, and caspase-1, and high levels of IL-10 and interferon (IFN)-β transcripts. Additionally, the mutants increased phosphorylation of STAT1, and decreased phosphorylation of STAT3. These findings suggest that MAPKs are associated with inflammasome activation in T. gondii-infected mice, which may contribute to new insight into the pathogenesis of T. gondii infection.
Insights
Mitogen-activated protein kinases (MAPKs) in Toxoplasma gondii are linked to inflammasome activation, impacting host resistance. Deleting these MAPKs in the parasite reduced virulence in mice, offering insights into infection pathogenesis.
Area of Science:
- Immunology
- Parasitology
- Molecular Biology
Background:
- Toxoplasma gondii infection activates NLRP1/3 inflammasomes, crucial for host defense.
- Mitogen-activated protein kinases (MAPKs) role in T. gondii pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the role of MAPK1 and MAPK2 in T. gondii virulence.
- To explore the association between MAPKs and inflammasome activation during T. gondii infection.
Main Methods:
- Deletion of MAPK1 and MAPK2 genes in type I T. gondii.
- Assessment of parasite virulence in mice.
- Quantification of host immune mediators including interleukins (IL-18, IL-10), inflammasome components (NLRP1/3, ASC, caspase-1), and interferon-beta (IFN-β).
- Analysis of STAT1 and STAT3 phosphorylation.
Main Results:
- Deletion of MAPK1/2 in T. gondii significantly decreased acute virulence in mice.
- Mutant parasites led to reduced levels of IL-18, NLRP1/3, ASC, and caspase-1.
- Elevated levels of IL-10 and IFN-β transcripts were observed in mice infected with MAPK mutants.
- MAPK deletion altered STAT1 and STAT3 phosphorylation patterns.
Conclusions:
- MAPKs in T. gondii are associated with inflammasome activation.
- MAPKs contribute to parasite virulence and modulation of host immune responses.
- These findings provide new insights into the pathogenesis of T. gondii infection.
