The use of transgenic parasites and host reporters to dissect the events that promote IL-12 production during toxoplasmosis

Infect Immun. 2014 Jul 14. pii: IAI.01643-14. [Epub ahead of print]

 

Christian DA¹, Koshy AA², Reuter MA³, Betts MR³, Boothroyd JC⁴, Hunter CA⁵.

 

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 latter events is unclear. Here, a reporter system using fluorescent parasite strains that inject Cre recombinase with their rhoptry proteins (Toxoplasma-Cre) were combined with Ai6 Cre reporter mice to identify cells that have been productively infected, 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 IL-12p40 that 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 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 are 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.
Copyright © 2014, American Society for Microbiology. All Rights Reserved.

PMID:

25024368

[PubMed - as supplied by publisher]