Use of transgenic parasites and host reporters to dissect events that promote interleukin-12 production during toxoplasmosis

David A. Christian, Anita A Koshy, Morgan A. Reuter, Michael R. Betts, John C. Boothroyd, Christopher A. Hunter

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The intracellular parasite Toxoplasma gondii has multiple strategies to alter host cell function, including the injection of rhoptry proteins into the cytosol of host cells as well as bystander populations, but the consequence of these events is unclear. Here, a reporter system using fluorescent parasite strains that inject Cre recombinase with their rhoptry proteins (Toxoplasma-Cre) was combined with Ai6 Cre reporter mice to identify cells that have been productively infected, that have been rhoptry injected but lack the parasite, or that have phagocytosed T. gondii. The ability to distinguish these host-parasite interactions was then utilized to dissect the events that lead to the production of interleukin-12 p40 (IL-12p40), which is required for resistance to T. gondii. In vivo, the use of invasion-competent or invasion-inhibited (phagocytosed) parasites with IL-12p40 (YET40) reporter mice revealed that dendritic cell (DC) and macrophage populations that phagocytose the parasite or are infected can express IL-12p40 but are not the major source, as larger numbers of uninfected cells secrete this cytokine. Similarly, the use of Toxoplasma-Cre parasite strains indicated that dendritic cells and inflammatory monocytes untouched by the parasite and not cells injected by the parasite are the primary source of IL-12p40. These results imply that a soluble host or parasite factor is responsible for the bulk of IL-12p40 production in vivo, rather than cellular interactions with T. gondii that result in infection, infection and clearance, injection of rhoptry proteins, or phagocytosis of the parasite.

Original languageEnglish (US)
Pages (from-to)4056-4067
Number of pages12
JournalInfection and Immunity
Volume82
Issue number10
DOIs
StatePublished - 2014

Fingerprint

Toxoplasmosis
Interleukin-12
Parasites
Toxoplasma
Phagocytosis
Dendritic Cells
Host-Parasite Interactions
Injections
Proteins
Infection
Cytosol
Population
Monocytes
Cell Count
Macrophages
adjuvant P40
Cytokines

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Use of transgenic parasites and host reporters to dissect events that promote interleukin-12 production during toxoplasmosis. / Christian, David A.; Koshy, Anita A; Reuter, Morgan A.; Betts, Michael R.; Boothroyd, John C.; Hunter, Christopher A.

In: Infection and Immunity, Vol. 82, No. 10, 2014, p. 4056-4067.

Research output: Contribution to journalArticle

Christian, David A. ; Koshy, Anita A ; Reuter, Morgan A. ; Betts, Michael R. ; Boothroyd, John C. ; Hunter, Christopher A. / Use of transgenic parasites and host reporters to dissect events that promote interleukin-12 production during toxoplasmosis. In: Infection and Immunity. 2014 ; Vol. 82, No. 10. pp. 4056-4067.
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