Externally triggered egress is the major fate of Toxoplasma gondii during acute infection

Tadakimi Tomita, Tatsuya Yamada, Louis M. Weiss, Amos Orlofsky

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

The apicomplexan parasite Toxoplasma gondii expands during acute infection via a cycle of invasion, intracellular replication, and lytic egress. Physiological regulation has not yet been demonstrated for either invasion or egress. We now report that, in contrast to cell culture systems, in which egress occurs only after five or more parasite divisions (2-3 days), intracellular residence is strikingly abbreviated in inflammatory cells in vivo, and early egress (after zero to two divisions) is the dominant parasite fate in acutely infected mice. Adoptive transfer experiments demonstrate rapid, reciprocal, kinetically uniform parasite transfer between donor and recipient compartments, with a t1/2 of ∼3 h. Inflammatory macrophages are major participants in this cycle of lytic egress and reinfection, which drives rapid macrophage turnover. Inflammatory triggering cells, principally macrophages, elicit egress in infected target macrophages, a process we term externally triggered egress (ETE). The mechanism of ETE does not require reactive oxygen or nitrogen species, the mitochondrial permeability transition pore, or a variety of signal transduction mediators, but is dependent on intracellular calcium and is highly sensitive to SB203580, an inhibitor of p38 MAPK as well as a related parasite-encoded kinase. SB203580 both inhibited the initiation of ETE and altered the progression of egress. Parasites recently completing a cycle of egress and reinfection were preferentially restricted in vivo, supporting a model in which ETE may favor host defense by a process of haven disruption. ETE represents a novel example of interaction between a parasite infectious cycle and host microenvironment.

Original languageEnglish (US)
Pages (from-to)6667-6680
Number of pages14
JournalJournal of Immunology
Volume183
Issue number10
DOIs
StatePublished - Nov 15 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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