Cutting edge: dendritic cells are essential for in vivo IL-12 production and development of resistance against Toxoplasma gondii infection in mice.
A powerful IFN-gamma 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-gamma 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-gamma-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.
Liu
Cheng-Hu
CH
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Fan
Yu-ting
YT
Dias
Alexandra
A
Esper
Lisia
L
Corn
Radiah A
RA
Bafica
Andre
A
Machado
Fabiana S
FS
Aliberti
Julio
J
D000208:Acute Disease; D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics; D019264:Adoptive Transfer; D000818:Animals; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000276:immunology; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D007113:Immunity, Innate / Q000235:genetics; D007165:Immunosuppression Therapy; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D053765:Interleukin-12 Subunit p35; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D053594:Myeloid Differentiation Factor 88; D021122:Protein Subunits / Q000172:deficiency / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D014122:Toxoplasma / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*
D048868:Adaptor Proteins, Signal Transducing; D000953:Antigens, Protozoan; D053765:Interleukin-12 Subunit p35; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D021122:Protein Subunits; C094052:soluble tachyzoite antigen, Toxoplasma gondii; D018664:Interleukin-12