Atrophy of skin-draining lymph nodes predisposes for impaired immune responses to secondary infection in mice with chronic intestinal nematode infection

PLoS Pathog. 2018 May 17;14(5):e1007008. doi: 10.1371/journal.ppat.1007008. eCollection 2018 May.


Intestinal nematodes suppress immune responses in the context of allergy, gut inflammation, secondary infection and vaccination. Several mechanisms have been proposed for this suppression including alterations in Th2 cell differentiation and increased Treg cell suppressive function. In this study, we show that chronic nematode infection leads to reduced peripheral responses to vaccination because of a generalized reduction in the available responsive lymphocyte pool. We found that superficial skin-draining lymph nodes (LNs) in mice that are chronically infected with the intestinal nematode Heligmosomides polygyrus, do not reach the same cellularity as worm-free mice upon subsequent BCG infection in the skin. B cells and T cells, all declined in skin-draining LN of H. polygyrus-infected mice, resulting in LNs atrophy and altered lymphocyte composition. Importantly, anti-helminthic treatment improved lymphocyte numbers in skin-draining LN, indicating that time after de-worming is critical to regain full-scale LN cellularity. De-worming, and time for the skin LN to recover cellularity, also mended responses to Bacille Calmette-Guerin (BCG) in the LN draining the footpad injection site. Thus, our findings show that chronic nematode infection leads to a paucity of lymphocytes in peripheral lymph nodes, which acts to reduce the efficacy of immune responses at these sites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrophy
  • BCG Vaccine / pharmacology
  • Female
  • Host-Pathogen Interactions / immunology
  • Immunocompromised Host / immunology
  • Lymph Nodes / immunology*
  • Lymph Nodes / pathology*
  • Lymphocyte Count
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nematospiroides dubius*
  • Skin / immunology*
  • Skin / pathology
  • Strongylida Infections / complications*
  • Strongylida Infections / drug therapy
  • Strongylida Infections / immunology*
  • T-Lymphocytes, Regulatory / immunology
  • Th2 Cells / immunology
  • Tuberculosis / etiology
  • Tuberculosis / immunology


  • BCG Vaccine

Grants and funding

SN received grants for this work from The Swedish Research Council / Vetenskapsrådet, VR grant no 348-2014-2819,; Stiftelsen Clas Groschinskys minne,; Åke Wibergs stiftelse ID3773405,; XF was supported by China Scholarship Council, The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.