| First Author | Kim L | Year | 2006 |
| Journal | J Immunol | Volume | 177 |
| Issue | 4 | Pages | 2584-91 |
| PubMed ID | 16888020 | Mgi Jnum | J:138352 |
| Mgi Id | MGI:3805057 | Doi | 10.4049/jimmunol.177.4.2584 |
| Citation | Kim L, et al. (2006) Toxoplasma gondii genotype determines MyD88-dependent signaling in infected macrophages. J Immunol 177(4):2584-91 |
| abstractText | Infection of mouse macrophages with Toxoplasma gondii elicits MAPK activation and IL-12 production, but host cell signaling pathways have not been clearly delineated. Here, we compared macrophage signaling in response to high virulence type I (RH) vs low virulence type II (ME49) strain infection. Tachyzoites of both strains induced p38 MAPK-dependent macrophage IL-12 release, although ME49 elicited 2- to 3-fold more cytokine than RH. IL-12 production was largely restricted to infected cells in each case. RH-induced IL-12 release did not require MyD88, whereas ME49-triggered IL-12 production was substantially dependent on this TLR/IL-1R adaptor molecule. MyD88 was also not required for RH-stimulated p38 MAPK activation, which occurred in the absence of detectable upstream p38 MAPK kinase activity. In contrast, ME49-driven p38 MAPK activation displayed an MyD88-dependent component. This parasite strain also induced MyD88-dependent activation of MKK4, an upstream activator of p38 MAPK. The results suggest that RH triggers MAPK activation and IL-12 production using MyD88-independent signaling, whereas ME49 uses these pathways as well as MyD88-dependent signaling cascades. Differences in host signaling pathways triggered by RH vs ME49 may contribute to the high and low virulence characteristics displayed by these parasite strains. |
