title: CD8α(+) dendritic cells are the critical source of interleukin-12 that controls acute infection by Toxoplasma gondii tachyzoites.
abstract: CD8α(+) dendritic cells (DCs) are important in vivo for cross-presentation of antigens derived from intracellular pathogens and tumors. Additionally, secretion of interleukin-12 (IL-12) by CD8α(+) DCs suggests a role for these cells in response to Toxoplasma gondii antigens, although it remains unclear whether these cells are required for protection against T. gondii infection. Toward this goal, we examined T. gondii infection of Batf3(-/-) mice, which selectively lack only lymphoid-resident CD8α(+) DCs and related peripheral CD103(+) DCs. Batf3(-/-) mice were extremely susceptible to T. gondii infection, with decreased production of IL-12 and interferon-γ. IL-12 administration restored resistance in Batf3(-/-) mice, and mice in which IL-12 production was ablated only from CD8α(+) DCs failed to control infection. These results reveal that the function of CD8α(+) DCs extends beyond a role in cross-presentation and includes a critical role for activation of innate immunity through IL-12 production during T. gondii infection.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Mona
authors.initials: M
authors.lastname: Mashayekhi
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Sandau
authors.forename: Ildiko R
authors.initials: IR
authors.lastname: Dunay
authors.forename: Eva M
authors.initials: EM
authors.lastname: Frickel
authors.forename: Asis
authors.initials: A
authors.lastname: Khan
authors.forename: Romina S
authors.initials: RS
authors.lastname: Goldszmid
authors.forename: Alan
authors.initials: A
authors.lastname: Sher
authors.forename: Hidde L
authors.initials: HL
authors.lastname: Ploegh
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Murphy
authors.forename: L David
authors.initials: LD
authors.lastname: Sibley
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
mesh_terms: D000208:Acute Disease; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics; D016827:CD8 Antigens / Q000096:biosynthesis; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004198:Disease Susceptibility / Q000276:immunology; D015536:Down-Regulation / Q000235:genetics; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D018664:Interleukin-12 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D012097:Repressor Proteins / Q000235:genetics; D014122:Toxoplasma / Q000276:immunology* / Q000472:pathogenicity; D014123:Toxoplasmosis / Q000276:immunology* / Q000382:microbiology; D014774:Virulence
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D012097:Repressor Proteins; C533289:SNFT protein, mouse; D018664:Interleukin-12; D007371:Interferon-gamma