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Phosphorylation of immunity-related GTPases by a Toxoplasma gondii-secreted kinase promotes macrophage survival and virulence.

Publication ,  Journal Article
Fentress, SJ; Behnke, MS; Dunay, IR; Mashayekhi, M; Rommereim, LM; Fox, BA; Bzik, DJ; Taylor, GA; Turk, BE; Lichti, CF; Townsend, RR; Qiu, W ...
Published in: Cell Host Microbe
December 16, 2010

Macrophages are specialized to detect and destroy intracellular microbes and yet a number of pathogens have evolved to exploit this hostile niche. Here we demonstrate that the obligate intracellular parasite Toxoplasma gondii disarms macrophage innate clearance mechanisms by secreting a serine threonine kinase called ROP18, which binds to and phosphorylates immunity-related GTPases (IRGs). Substrate profiling of ROP18 revealed a preference for a conserved motif within switch region I of the GTPase domain, a modification predicted to disrupt IRG function. Consistent with this, expression of ROP18 was both necessary and sufficient to block recruitment of Irgb6, which was in turn required for parasite destruction. ROP18 phosphorylation of IRGs prevented clearance within inflammatory monocytes and IFN-γ-activated macrophages, conferring parasite survival in vivo and promoting virulence. IRGs are implicated in clearance of a variety of intracellular pathogens, suggesting that other virulence factors may similarly thwart this innate cellular defense mechanism.

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Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

December 16, 2010

Volume

8

Issue

6

Start / End Page

484 / 495

Location

United States

Related Subject Headings

  • Virulence
  • Toxoplasma
  • Protozoan Proteins
  • Protein Serine-Threonine Kinases
  • Phosphorylation
  • Mice
  • Macrophages
  • Immunology
  • Immunity, Innate
  • GTP-Binding Proteins
 

Citation

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Fentress, S. J., Behnke, M. S., Dunay, I. R., Mashayekhi, M., Rommereim, L. M., Fox, B. A., … Sibley, L. D. (2010). Phosphorylation of immunity-related GTPases by a Toxoplasma gondii-secreted kinase promotes macrophage survival and virulence. Cell Host Microbe, 8(6), 484–495. https://doi.org/10.1016/j.chom.2010.11.005
Fentress, Sarah J., Michael S. Behnke, Ildiko R. Dunay, Mona Mashayekhi, Leah M. Rommereim, Barbara A. Fox, David J. Bzik, et al. “Phosphorylation of immunity-related GTPases by a Toxoplasma gondii-secreted kinase promotes macrophage survival and virulence.Cell Host Microbe 8, no. 6 (December 16, 2010): 484–95. https://doi.org/10.1016/j.chom.2010.11.005.
Fentress SJ, Behnke MS, Dunay IR, Mashayekhi M, Rommereim LM, Fox BA, et al. Phosphorylation of immunity-related GTPases by a Toxoplasma gondii-secreted kinase promotes macrophage survival and virulence. Cell Host Microbe. 2010 Dec 16;8(6):484–95.
Fentress, Sarah J., et al. “Phosphorylation of immunity-related GTPases by a Toxoplasma gondii-secreted kinase promotes macrophage survival and virulence.Cell Host Microbe, vol. 8, no. 6, Dec. 2010, pp. 484–95. Pubmed, doi:10.1016/j.chom.2010.11.005.
Fentress SJ, Behnke MS, Dunay IR, Mashayekhi M, Rommereim LM, Fox BA, Bzik DJ, Taylor GA, Turk BE, Lichti CF, Townsend RR, Qiu W, Hui R, Beatty WL, Sibley LD. Phosphorylation of immunity-related GTPases by a Toxoplasma gondii-secreted kinase promotes macrophage survival and virulence. Cell Host Microbe. 2010 Dec 16;8(6):484–495.
Journal cover image

Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

December 16, 2010

Volume

8

Issue

6

Start / End Page

484 / 495

Location

United States

Related Subject Headings

  • Virulence
  • Toxoplasma
  • Protozoan Proteins
  • Protein Serine-Threonine Kinases
  • Phosphorylation
  • Mice
  • Macrophages
  • Immunology
  • Immunity, Innate
  • GTP-Binding Proteins