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An essential role for TH2-type responses in limiting acute tissue damage during experimental helminth infection

Nature Medicine volume 18, pages 260–266 (2012)Cite this article

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Abstract

Helminths induce potent T helper 2 (TH2)-type immune responses that can mediate worm expulsion, but the role of this response in controlling the acute tissue damage caused by migrating multicellular parasites through vital tissues remains uncertain. We used a helminth infection model in which parasitic nematode larvae migrate transiently through the lung, resulting in hemorrhage and inflammation. We found that IL-17 initially contributed to inflammation and lung damage, whereas subsequent IL-4 receptor (IL-4R) signaling reduced elevations in IL-17 mRNA levels, enhanced the expression of insulin-like growth factor 1 (IGF-1) and IL-10 and stimulated the development of M2 macrophages, all of which contributed to the rapid resolution of tissue damage. These studies indicate an essential role for TH2-type immune responses in mediating acute wound healing during helminth infection.

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Figure 1: Kinetics of N. brasiliensis–induced lung damage.
Figure 2: IL-4R signaling controls acute lung hemorrhaging and IL-17–dependent neutrophil infiltration.
Figure 3: Blockade of IL-4R–dependent IGF-1 signaling inhibits control of inflammation and hemorrhaging in N. brasiliensis–inoculated mice.
Figure 4: IL-10 downregulates lung inflammation and elevations in Il17 mRNA level in N. brasiliensis–inoculated mice.
Figure 5: Macrophages control both lung hemorrhaging and inflammation during infection with N. brasiliensis.
Figure 6: Model of acute resolution of lung damage mediated by a helminth-induced TH2-type response.

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Acknowledgements

This work was supported by US National Institutes of Health grants AI031678.

Author information

Author notes

  1. Zhugong Liu

    Present address: Present address: Food and Drug Administration, Center for Biologics Evaluation and Research/Office of Blood Research and Review/Division of Blood Applications, Laboratory of Immunohematology and Molecular Testing, Rockville, Maryland, USA.,

  2. Fei Chen and Zhugong Liu: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine and Center for Immunity and Inflammation, New Jersey Medical School, University of Medicine & Dentistry of New Jersey, Newark, New Jersey, USA

    Fei Chen, Zhugong Liu, Wenhui Wu, Cristina Rozo, Scott Bowdridge, Ariel Millman & William C Gause

  2. Department of Molecular Cell Biology, Vrije Universiteit, Vrije Universiteit Medical Center, Amsterdam, The Netherlands

    Nico Van Rooijen

  3. US Department of Agriculture, Agricultural Research Service, Beltsville Human Nutrition Research Center, Diet, Genomics, and Immunology Laboratory, Beltsville, Maryland, USA

    Joseph F Urban Jr

  4. Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland, USA

    Thomas A Wynn

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Contributions

F.C. performed the majority of the experiments and contributed to experimental design. Z.L. contributed to the initial experimental design and essential experiments before leaving the laboratory. W.W. performed experiments with F.C., particularly the flow cytometry experiments, and contributed to the experimental design. C.R. performed experiments with Z.L. and F.C. and contributed to the experimental design. S.B. performed experiments with F.C. and helped develop techniques for tracking parasites. A.M. performed experiments with F.C., maintained and genotyped mouse strains and also prepared parasites for inoculation. N.V.R. provided fresh clodronate liposomes for in vivo experiments and provided advice for use of this reagent for macrophage depletion. J.F.U. maintained parasite stocks and provided them as needed and gave crucial input to the experimental design. T.A.W. provided immunodeficient mice for experiments and gave important input to the experimental design and writing of the paper. W.C.G. designed most of research project, provided oversight of experiments and wrote the majority of the paper.

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Correspondence to William C Gause.

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Chen, F., Liu, Z., Wu, W. et al. An essential role for TH2-type responses in limiting acute tissue damage during experimental helminth infection. Nat Med 18, 260–266 (2012). https://doi.org/10.1038/nm.2628

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