Cutting Edge: Dendritic Cells Are Essential for In Vivo IL-12 Production and Development of Resistance againstToxoplasma gondiiInfection in Mice

Abstract

A powerful IFN-γ response is triggered upon infection with the protozoan parasite, Toxoplasma gondii. Several cell populations, including dendritic cells (DCs), macrophages, and neutrophils, produce IL-12, a key cytokine for IFN-γ induction. However, it is still unclear which of the above cell populations is its main source. Diphtheria toxin (DT) injection causes transient DC depletion in a transgenic mouse expressing Simian DT receptors under the control of the CD11c promoter, allowing us to investigate the role of DCs in IL-12 production. T. gondii-inoculated DT-treated and control groups were monitored for IL-12 levels and survival. We show in this study that DC depletion abolished IL-12 production and led to mortality. Furthermore, replenishment with wild-type, but not MyD88- or IL-12p35-deficient, DCs rescued IL-12 production, IFN-γ-induction, and resistance to infection in DC-depleted mice. Taken together, the results presented in this study indicate that DCs constitute the major IL-12-producing cell population in vivo during T. gondii infection.

A comparative study between excretory/secretory and autoclaved vaccines against RH strain of Toxoplasma gondii in murine models

“…In addition to increasing the strength and kinetics of an immune response, they also play a role in determining both the type of immune response generated and the potential application in animals and humans (Cox and Coulter 1997;MartinezGómez et al 2009). As the main protection in toxoplasmosis, is carried out by the cellular arm of the immune response (Liu et al 2006), therefore, the use of a Th1-driving adjuvant can cause better enhancement of the vaccine efficacy via stimulating IL-12 production by macrophages (Yap et al 2000). In this study, BCG was used as an adjuvant in an attempt to enhance the efficacy of the Toxoplasma vaccine.…”

IL-12 Signaling Drives CD8+ T Cell IFN-γ Production and Differentiation of KLRG1+ Effector Subpopulations during Toxoplasma gondii Infection

“…Thus, the spectrum of innate mediators induced by different microbial agents might govern the requirements for individual signal 3 cytokines for the generation of pathogen-specific CTL responses (17). Because the production of type 1 IFNs in response to Toxoplasma infection has not been reported and a hallmark of toxoplasmosis is the production of IL-12 by dendritic cells (18) and macrophages (19), IL-12 emerges as the prime candidate signal 3 cytokine in this infection. From previous studies using in vivo IL-12 neutralizing Abs (19,20) and mice genetically deficient in the p40 subunit of IL-12 (21)(22)(23), it remains unclear to what extent an IL-12 signaling deficiency impacts CTL effector differentiation during T. gondii infection.…”

PD-1 on dendritic cells impedes innate immunity against bacterial infection

“…The temporary depletion of DCs abolished IL-12 production and increased early mortality. 9 Furthermore, CD8␣ ϩ DCs were found to be essential for efficient LM entry into the spleen. 10 With the importance of DCs for early host defense against pathogens demonstrated, the molecular mechanisms regulating activated DCs during an innate response, however, still remain largely unknown.…”