Article

ILC2s and T cells cooperate to ensure maintenance of M2 macrophages for lung immunity against hookworms

  • Nature Communications 6, Article number: 6970 (2015)
  • doi:10.1038/ncomms7970
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Abstract

Defining the immune mechanisms underlying protective immunity to helminth infection remains an important challenge. Here we report that lung CD4+ T cells and Group 2 innate lymphoid cells (ILC2s) work in concert to block Nippostrongylus brasiliensis (Nb) development in the parenchyma within 48 h in mice. Immune-damaged larvae have a striking morphological defect that is dependent on the expansion of IL-13-producing ILC2 and CD4+ T cells, and the activation of M2 macrophages. This T-cell requirement can be bypassed by administration of IL-2 or IL-33, resulting in expansion of IL-13-producing ILC2s and larval killing. Depletion of ILC2s inhibits larval killing in IL-2-treated mice. Our results broaden understanding of ILC2’s role in immunity to helminths by demonstrating that they not only act as alarmin sensors, but can also be sustained by CD4+ T cells, ensuring both the prompt activation and the maintenance of IL-13-dependent M2 macrophage immunity in the lung.

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Acknowledgements

We thank William E Paul for the 4C13R mice. We thank the Malaghan BRU for animal husbandry, the Hugh Green Cytometry Core for help with the cytometry and the microscopy and Prof Franca Ronchese for her thoughtful comments on the manuscript. The Health Research Council of New Zealand and the Marjorie Barclay Trust supported this work. This work was also supported by National Health and Medical Research Council grant APP1047041 to W.W. This research was sponsored and funded by AbbVie Inc (anti-IL-13 antibody). This work was also supported by the Wellington Medical Research Foundation Inc.

Author information

Author notes

    • Tiffany Bouchery
    •  & Ryan Kyle

    These authors contributed equally to this work

Affiliations

  1. Malaghan Institute of Medical Research, Wellington 6242, New Zealand

    • Tiffany Bouchery
    • , Ryan Kyle
    • , Mali Camberis
    • , Amy Shepherd
    • , Kara Filbey
    • , Alexander Smith
    • , Elizabeth Forbes-Blom
    •  & Graham Le Gros
  2. School of Biological Sciences, Victoria University of Wellington, Wellington 6012, New Zealand

    • Ryan Kyle
  3. Queensland University of Technology, Brisbane, Queensland 4000, Australia

    • Marina Harvie
  4. The Ferrier Research Institute, Victoria University of Wellington, Lower Hutt, Wellington 5010, New Zealand

    • Gavin Painter
    •  & Karen Johnston
  5. Department of Pathology and Molecular Medicine, University of Otago, Wellington 6242, New Zealand

    • Peter Ferguson
    •  & Brett Delahunt
  6. The Centenary Institute, Sydney, New South Wales 2050, Australia

    • Rohit Jain
    • , Ben Roediger
    •  & Wolfgang Weninger
  7. Discipline of Dermatology, Sydney Medical School, Sydney, New South Wales 2052, Australia

    • Rohit Jain
    • , Ben Roediger
    •  & Wolfgang Weninger
  8. Department of Dermatology, Royal Prince Alfred Hospital, Camperdown, New South Wales 2050, Australia

    • Wolfgang Weninger

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Contributions

T.B., R.K., E.FB., M.C. and G.LG. conceived of the idea for this project and participated in the writing of the paper; T.B., R.K. and K.F. performed the immunology and flow cytometry experiments; M.C. and T.B. provided expertise in parasitology and performed worm count experiments; T.B. designed and performed imaging experiments; W.W., R.J. and B.R contributed to experimental design and discussion; G.P. and K.J. prepared chemicals, such as clodronate liposomes and BEC. P.F. and B.D, provided expertise in immunopathology. A.A.T.S. performed advanced statistical analyses. All authors discussed the results and commented on the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Graham Le Gros.

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    Supplementary Figures 1-7

Videos

  1. 1.

    Supplementary Movie 1

    Z-stack of lungs infected with CFSE-labeled Nb. PKH26-labeled bone marrow-derived M2 macrophages were intranasally transferred one day before intravenous inoculation of Nb. Images were acquired on live lung tissue, 24 hours after infection.

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