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Forward Genetics Screens Using Macrophages to Identify Toxoplasma gondii Genes Important for Resistance to IFN-γ-Dependent Cell Autonomous Immunity
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Toxoplasma co-opts host cells it does not invade

Anita A Koshy1, Hans K Dietrich, David A Christian

  • 1Department of Medicine (Infectious Disease), Stanford University School of Medicine, Stanford, California, United States of America.

Plos Pathogens
|August 23, 2012
PubMed

Insights

Toxoplasma gondii injects effector proteins into host cells, even without successful invasion. These injected proteins manipulate uninfected cells, impacting host manipulation strategies for intracellular microbes.

Area of Science:

  • Microbiology
  • Cell Biology
  • Parasitology

Background:

  • Intracellular microbes like Toxoplasma gondii inject effector proteins into host cells.
  • Rhoptry-secreted proteins are crucial for parasite manipulation.
  • Rhoptry discharge was thought to occur only during successful host cell invasion.

Purpose of the Study:

  • To investigate whether Toxoplasma gondii injects rhoptry proteins into cells without successful invasion.
  • To determine if these injected proteins can manipulate uninfected cells.
  • To quantify the prevalence of uninfected-injected cells in vivo.

Main Methods:

  • Utilized reporter systems to track rhoptry protein injection.
  • Employed a Cre-reporter mouse model with a Toxoplasma-Cre strain.
  • Analyzed infected and uninfected cells in mouse brains.

Main Results:

  • Demonstrated in vitro injection of rhoptry proteins into non-productively invaded cells.
  • Showed that these proteins can manipulate uninfected cells similarly to infected cells.
  • Revealed that uninfected-injected cells are more prevalent than infected-injected cells in the mouse brain.

Conclusions:

  • Toxoplasma gondii actively injects effector proteins into host cells, irrespective of successful invasion.
  • This injection mechanism allows manipulation of uninfected cells, broadening the parasite's impact.
  • The findings suggest a novel host manipulation strategy for intracellular microbes and have implications for understanding Toxoplasma persistence.

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