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CD8 alpha(+) Dendritic Cells Are the Critical Source of Interleukin-12 that Controls Acute Infection by Toxoplasma gondii Tachyzoites

  1. Author:
    Mashayekhi, M.
    Sandau, M. M.
    Dunay, I. R.
    Frickel, E. M.
    Khan, A.
    Goldszmid, R. S.
    Sher, A.
    Ploegh, H. L.
    Murphy, T. L.
    Sibley, L. D.
    Murphy, K. M.

  2. Author Address

    [Mashayekhi, M; Sandau, MM; Murphy, TL; Murphy, KM] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Dunay, IR; Khan, A; Sibley, LD] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. [Murphy, KM] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA. [Frickel, EM; Ploegh, HL] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Goldszmid, RS; Sher, A] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Goldszmid, RS] NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.;Murphy, KM (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA;kmurphy@pathology.wustl.edu
    1. Year: 2011
    2. Date: Aug
  2. Journal: Immunity
    1. 35
    2. 2
    3. Pages: 249-259
  4. Type of Article: Article
  5. ISSN: 1074-7613
  1. Abstract:

    CD8 alpha(+) 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 CD8 alpha(+) 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 CD8 alpha(+) DCs and related peripheral CD103(+) DCs. Batf3(-/-) mice were extremely susceptible to T. gondii infection, with decreased production of IL-12 and interferon-gamma. IL-12 administration restored resistance in Batf3(-/-) mice, and mice in which IL-12 production was ablated only from CD8 alpha(+) DCs failed to control infection. These results reveal that the function of CD8 alpha(+) 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.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.immuni.2011.08.008
  3. View record in Web of Science®
  4. WOS: 000294387900014

Library Notes

  1. Fiscal Year: FY2010-2011
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