Plasmacytoid Dendritic Cells Are Activated by Toxoplasma gondii to Present Antigen and Produce Cytokines

Abstract

Infection with the parasite Toxoplasma gondii leads to the induction of a Th1-type response dominated by IFN-γ production and control of this pathogen. Cells of the innate immune system are essential in initiating this response both through the production of IL-12 as well as the presentation of parasite-derived Ags to MHC-restricted T cells. Although dendritic cells (DCs) have been implicated in these events, the contribution of individual DC populations remains unclear. Therefore, multiparameter flow cytometry was used to identify and characterize subsets of murine DCs during acute toxoplasmosis. This approach confirmed that infection leads to the expansion and activation of conventional DC (cDC) subsets. Unexpectedly, however, this analysis further revealed that plasmacytoid DCs are also expanded and that these cells up-regulate MHC class II and costimulatory molecules associated with their acquired ability to prime naive CD4+ T cells. Furthermore, T. gondii-activated plasmacytoid DCs produce high levels of IL-12 and both plasmacytoid DC maturation and cytokine production are dependent on TLR11. Together these studies suggest that pDCs are a prominent DC subset involved in the initial stages of T. gondii infection, presenting parasite Ags and producing cytokines that are important for controlling infection.

Functional Dissection of Toxoplasma gondii Perforin-like Protein 1 Reveals a Dual Domain Mode of Membrane Binding for Cytolysis and Parasite Egress

“…The RH⌬ku80⌬hxg, RH⌬ku80⌬plp1 strains were transfected with 50 g of the dsRed expression plasmid (46), linearized within the tub promoter, and cloned by limiting dilution. DsRed strains were maintained with chloramphenicol selection.…”

Cutting Edge: PulmonaryLegionella pneumophilaIs Controlled by Plasmacytoid Dendritic Cells but Not Type I IFN

“…One alternative mechanism is that pDCs produce cytokines other than IFN-I that can be used to combat bacteria. Little attention has been paid to pDC cytokine production other than IFN-I, but pDCs do produce IL-12 (18,34), and pDCs deficient in IL-18 production are unable to stimulate IFN-g production in HSV infection (35). It will be important to look at the full gamut of cytokines produced by pDCs in response to infectious agents, especially IL-12 and IL-18, both of which have been shown to be important in controlling L. pneumophila infection (33,36).…”

“…pDCs also produce IFN-I when exposed to Borrelia burgdorferi in vitro (17). Finally, pDCs can activate CD4 T cells via Ag presentation and secretion of IL-12 in response to Toxoplasma gondii infection (18). As IFN-I may also be an effector molecule used in the clearance of intracellular bacterial infections, such as L. pneumophila, we studied the role of pDCs in a mouse model of L. pneumophila infection.…”

Major Role for CD8+T Cells in the Protection Against Toxoplasma gondii Following Dendritic Cell Vaccination

“…Indeed, IL-12 is a major cytokine secreted in response to T. gondii by neutrophils 23 , macrophages 24 , plasmacytoid dendritic cells (pDCs) 25 , conventional dendritic cells (cDCs) 26 and the subset of cDCs expressing CD8 27 . Recently Mashayekhi et al have demonstrated the critical role of CD8+ DCs for activation of innate immunity through IL-12 production during T. gondii infection and have shown that CD8+ DCs are the only cells whose IL-12 production is required to control acute infection 28 .…”