The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Strain-specific activation of the NF-κB pathway by GRA15, a novel Toxoplasma gondii dense granule protein
Open accessAbstract
NF-κB is an integral component of the immune response to Toxoplasma gondii. Although evidence exists that T. gondii can directly modulate the NF-κB pathway, the parasite-derived effectors involved are unknown. We determined that type II strains of T. gondii activate more NF-κB than type I or type III strains, and using forward genetics we found that this difference is a result of the polymorphic protein GRA15, a novel dense granule protein which T. gondii secretes into the host cell upon invasion. A GRA15-deficient type II strain has a severe defect in both NF-κB nuclear translocation and NF-κB–mediated transcription. Furthermore, human cells expressing type II GRA15 also activate NF-κB, demonstrating that GRA15 alone is sufficient for NF-κB activation. Along with the rhoptry protein ROP16, GRA15 is responsible for a large part of the strain differences in the induction of IL-12 secretion by infected mouse macrophages. In vivo bioluminescent imaging showed that a GRA15-deficient type II strain grows faster compared with wild-type, most likely through its reduced induction of IFN-γ. These results show for the first time that a dense granule protein can modulate host signaling pathways, and dense granule proteins can therefore join rhoptry proteins in T. gondii’s host cell–modifying arsenal.
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Mootha, V. K., Lindgren, C. M., Eriksson, K.-F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197
TM4: a free, open-source system for microarray data management and analysis
Saeed, A. I., Sharov, V., White, J., Li, J., Liang, W., Bhagabati, N., Braisted, J., Klapa, M., Currier, T., Thiagarajan, M., et al. (2003) · BioTechniques · doi:10.2144/03342mt01 · Cited by 4,837
NF-κB regulation in the immune system
Li, Q., & Verma, I. M. (2002) · Nature Reviews Immunology · doi:10.1038/nri910 · Cited by 4,007
Hayden, M. S., & Ghosh, S. (2004) · Genes & Development · doi:10.1101/gad.1228704 · Cited by 3,842
Missing Pieces in the NF-κB Puzzle
Ghosh, S., & Karin, M. (2002) · Cell · doi:10.1016/s0092-8674(02)00703-1 · Cited by 3,638 · cited 1×
“IKK- has greater kinase activity than IKK- and is the principal kinase responsible for the phosphorylation of IB (Ghosh and Karin, 2002; Li and Verma, 2002).”
BackgroundInterleukin-4/STAT6 Represses STAT1 and NF-κB-dependent Transcription through Distinct Mechanisms
Ohmori, Y., & Hamilton, T. A. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m006227200 · Cited by 106
Cited by
Toxoplasma Effectors Targeting Host Signaling and Transcription
Hakimi, M.-A., Olias, P., & Sibley, L. D. (2017) · Clinical Microbiology Reviews · doi:10.1128/cmr.00005-17 · Cited by 339
Modulators of the Balance between M1 and M2 Macrophages during Pregnancy
Zhang, Y.-H., He, M., Wang, Y., & Liao, A.-H. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00120 · Cited by 292
Gold, D. A., Kaplan, A. D., Lis, A., Bett, G. C. L., Rosowski, E. E., Cirelli, K. M., Bougdour, A., Sidik, S. M., Beck, J. R., Lourido, S., et al. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.04.003 · Cited by 268
Self-citationFox, B. A., Guevara, R. B., Rommereim, L. M., Falla, A., Bellini, V., Pètre, G., Rak, C., Cantillana, V., Dubremetz, J.-F., Cesbron-Delauw, M.-F., et al. (2019) · mBio · doi:10.1128/mbio.00589-19 · Cited by 89
Niedelman, W., Sprokholt, J. K., Clough, B., Frickel, E.-M., & Saeij, J. P. J. (2013) · Infection and Immunity · doi:10.1128/iai.00416-13 · Cited by 81
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Metadata
- Authors
- Rosowski, E. E., Lu, D., Julien, L., Rodda, L., Gaiser, R. A., Jensen, K. D. C., & Saeij, J. P. J.
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2011-01-03
- Volume
- 208
- Issue
- 1
- Pages
- 195-212
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2074177784
- Cited by
- 416
- References
- 7
- FWCI
- 21.34
- Type
- journal article
- Language
- en
- Open access
- bronze
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- The paper
- Rosowski, E. E., Lu, D., Julien, L., Rodda, L., Gaiser, R. A., Jensen, K. D. C., & Saeij, J. P. J. (2011). Strain-specific activation of the NF-κB pathway by GRA15, a novel Toxoplasma gondii dense granule protein. Journal of Experimental Medicine. https://doi.org/10.1084/jem.20100717
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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