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PMID: 21867928 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

CD8α(+) dendritic cells are the critical source of interleukin-12 that controls acute infection by Toxoplasma gondii tachyzoites.

Immunity ·Vol. 35 ·No. 2 ·2011-08-26 ·Pages 249-59

Mashayekhi M, Sandau MM, Dunay IR, Frickel EM, Khan A, Goldszmid RS, Sher A, Ploegh HL, Murphy TL, Sibley LD, Murphy KM

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.

MeSH Terms
Acute Disease Animals Basic-Leucine Zipper Transcription Factors/genetics CD8 Antigens/biosynthesis Cells, Cultured Dendritic Cells/drug effects,immunology,metabolism,pathology Disease Susceptibility/immunology Down-Regulation/genetics Immunity, Innate Interferon-gamma/genetics,metabolism Interleukin-12/administration & dosage,genetics,immunology,metabolism Mice Mice, Inbred Strains Mice, Knockout Repressor Proteins/genetics Toxoplasma/immunology,pathogenicity Toxoplasmosis/immunology,microbiology Virulence
Chemicals
Basic-Leucine Zipper Transcription Factors CD8 Antigens CD8 antigen, alpha chain Repressor Proteins SNFT protein, mouse Interleukin-12 Interferon-gamma
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Mashayekhi Mona
Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Sandau Michelle M
Dunay Ildiko R
Frickel Eva M
Khan Asis
Goldszmid Romina S
Sher Alan
Ploegh Hidde L
Murphy Theresa L
Sibley L David
Murphy Kenneth M
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2011.08.008
Published
2011-08-26
Pages
249-59
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC3171793
Subset
IM
Grants
Howard Hughes Medical Institute · United States
NIAID NIH HHS · R01 AI036629 · United States
NIAID NIH HHS · R01 AI059176 · United States
NIAID NIH HHS · AI059176 · United States
Corrections
CommentIn
PMID: 21867923
External Links
PubMed source DOI: 10.1016/j.immuni.2011.08.008 PMC Full Text View journal details
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