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Mast cell–derived tumor necrosis factor induces hypertrophy of draining lymph nodes during infection

Nature Immunology volume 4, pages 1199–1205 (2003)Cite this article

Abstract

Palpable swelling of regional lymph nodes is a common sequela of microbial infections but the mechanism responsible for the sequestration and subsequent coordination of lymphocyte responses within these dynamic structures remains poorly understood. Here we show that draining lymph nodes of mast cell–deficient mice did not demonstrate swelling after intradermal bacterial challenge. Testing of individual mast cell–derived products in this model indicated that tumor necrosis factor was the main mediator of nodal hypertrophy, whereas tryptase and histamine had no effect. After peripheral mast cell activation, both tumor necrosis factor concentrations and the recruitment of circulating T cells were increased within draining nodes. These results show a critical function for peripheral mast cell–derived tumor necrosis factor in regulating the hypertrophy of draining lymph nodes during infection.

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Figure 1: Lymph node hypertrophy after bacterial infection.
Figure 2: Quantification of local mast cell numbers in footpads after infection.
Figure 3: Regulation of lymph node hypertrophy by mast cells and mast cell–derived TNF during infection.
Figure 4: Regulation of lymph node hypertrophy by mast cell–derived TNF.
Figure 5: TNF accumulation in lymph nodes after bacterial infection or specific mast cell activation.
Figure 6: Mast cell–mediated lymph node hypertrophy involves increased sequestration of T cells and increased expression of VCAM-1 in lymph nodes.

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Acknowledgements

We thank M. Yanagita, R. Goyal, the Duke Photopath Lab and the Duke Human Vaccine Institute Flow Cytometry Core Facility for their assistance with experiments. Supported by funds from the National Institutes of Health and from the Sandler Foundation for Asthma Research.

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Authors and Affiliations

  1. Department of Pathology, Duke University Medical Center, Durham, 27710, North Carolina, USA

    James B McLachlan, Justin P Hart, Salvatore V Pizzo, Christopher P Shelburne, Herman F Staats & Soman N Abraham

  2. Department of Immunology, Duke University Medical Center, Durham, 27710, North Carolina, USA

    Michael D Gunn & Soman N Abraham

  3. Department of Medicine, Duke University Medical Center, Durham, 27710, North Carolina, USA

    Herman F Staats & Michael D Gunn

  4. Department of Molecular Genetics & Microbiology, Duke University Medical Center, Durham, 27710, North Carolina, USA

    Soman N Abraham

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  1. James B McLachlan
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Correspondence to Soman N Abraham.

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McLachlan, J., Hart, J., Pizzo, S. et al. Mast cell–derived tumor necrosis factor induces hypertrophy of draining lymph nodes during infection. Nat Immunol 4, 1199–1205 (2003). https://doi.org/10.1038/ni1005

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