Neurons are the Primary Target Cell for the Brain-Tropic Intracellular Parasite Toxoplasma gondii

Carla M. Cabral, Shraddha Tuladhar, Hans K. Dietrich, Elizabeth Nguyen, Wes R. MacDonald, Tapasya Trivedi, Asha Devineni, Anita A. Koshy

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

Toxoplasma gondii, a common brain-tropic parasite, is capable of infecting most nucleated cells, including astrocytes and neurons, in vitro. Yet, in vivo, Toxoplasma is primarily found in neurons. In vitro data showing that interferon-γ-stimulated astrocytes, but not neurons, clear intracellular parasites suggest that neurons alone are persistently infected in vivo because they lack the ability to clear intracellular parasites. Here we test this theory by using a novel Toxoplasma-mouse model capable of marking and tracking host cells that directly interact with parasites, even if the interaction is transient. Remarkably, we find that Toxoplasma shows a strong predilection for interacting with neurons throughout CNS infection. This predilection remains in the setting of IFN-γ depletion; infection with parasites resistant to the major mechanism by which murine astrocytes clear parasites; or when directly injecting parasites into the brain. These findings, in combination with prior work, strongly suggest that neurons are not incidentally infected, but rather they are Toxoplasma’s primary in vivo target.

Original languageEnglish (US)
Article numbere1005447
JournalPLoS pathogens
Volume12
Issue number2
DOIs
StatePublished - Feb 2016

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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