The immune system utilizes two distinct effector mechanisms of T cells depending on two different life cycle stages of a single pathogen, Toxoplasma gondii, to control its cerebral infection

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22 Scopus citations

Abstract

Toxoplasma gondii takes two different life cycle stages within intermediate hosts including humans. Tachyzoites proliferate during the acute stage, and they transform into cysts to establish a chronic infection preferentially in the brain. IFN-γ production by infiltrated CD4+ and CD8+ T cells is required for the prevention of cerebral tachyzoite growth. IFN-γ production by brain-resident cells, most likely microglia, plays a key first line defense role to facilitate both innate and T cell-mediated protective immunity to control the tachyzoite growth. IFN-γ produced by brain-resident cells activates cerebral expression of IFN-dependent effector molecules to suppress tachyzoite growth during the early stage of infection. Their IFN-γ production also induces an expression of CXCL9 and CXCL10 chemokines to recruit immune T cells into the brain, and upregulates cerebral expression of MHC class I and II molecules for antigen presentation to the recruited T cells to activate their IFN-γ production. CD8+ T cells also have the activity to remove T. gondii cysts from the brains of infected hosts. Of interest, the anti-cyst activity of CD8+ T cells does not require their IFN-γ but does require perforin. Notably, we discovered that CD8+ cytotoxic T cells penetrate in the cysts in a perforin-mediated manner, which induces morphological deterioration and destruction of the cysts and an accumulation of microglia and macrophages for their elimination. Thus, the immune system employs two distinct effector mechanisms mediated by IFN-γ or perforin depending on two different life cycle stages of a single pathogen, T. gondii, to control its cerebral infection.

Original languageEnglish
Article number102030
JournalParasitology International
Volume76
DOIs
StatePublished - Jun 2020

Bibliographical note

Publisher Copyright:
© 2019 Elsevier B.V.

Keywords

  • Cysts
  • IFN-γ
  • Perforin
  • T cell invasion
  • Tachyzoite
  • Toxoplasma

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

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