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Toll-like receptors control activation of adaptive immune responses

Nature Immunology volume 2, pages 947–950 (2001)Cite this article

Abstract

Mechanisms that control the activation of antigen-specific immune responses in vivo are poorly understood. It has been suggested that the initiation of adaptive immune responses is controlled by innate immune recognition. Mammalian Toll-like receptors play an essential role in innate immunity by recognizing conserved pathogen-associated molecular patterns and initiating the activation of NF-κB and other signaling pathways through the adapter protein, MyD88. Here we show that MyD88-deficient mice have a profound defect in the activation of antigen-specific T helper type 1 (TH1) but not TH2 immune responses. These results suggest that distinct pathways of the innate immune system control activation of the two effector arms of adaptive immunity.

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Figure 1: MyD88-deficient lymphocytes had no intrinsic defects in development and function.
Figure 2: Antigen-specific TH1 cell responses were impaired in MyD88-deficient mice.
Figure 3: Antigen-specific TH2-dependent immunoglobulin production was independent of MyD88.
Figure 4: Increased antigen-specific IL-13 production in MyD88-deficient lymph node cells.
Figure 5: Maturation of dendritic cells by mycobacteria requires MyD88.

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Acknowledgements

We thank C. A. Janeway and R. A. Flavell for the 1H3.1 TCR–transgenic and caspase-1–deficient mice, respectively. R. M. thanks C. A. Janeway for critical reading of the manuscript and continuous support. Supported by Howard Hughes Medical Institute, NIH (AI44220-01) and Searle (to R. M.) and by Deutsche Forschungsgemeinschaft (to M. S.).

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  1. Markus Schnare and Gregory M. Barton: These authors contributed equally to this work.

Authors and Affiliations

  1. Section of Immunobiology, Yale University School of Medicine, New Haven, 06520, CT, USA

    Markus Schnare, Gregory M. Barton, Agnieszka Czopik Holt & Ruslan Medzhitov

  2. Howard Hughes Medical Institute, New Haven, 06520, CT, USA

    Markus Schnare, Gregory M. Barton & Ruslan Medzhitov

  3. Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, 565-0871, Osaka, Japan

    Kiyoshi Takeda & Shizuo Akira

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  1. Markus Schnare
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Correspondence to Ruslan Medzhitov.

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Schnare, M., Barton, G., Holt, A. et al. Toll-like receptors control activation of adaptive immune responses. Nat Immunol 2, 947–950 (2001). https://doi.org/10.1038/ni712

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