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Neutrophils prime a long-lived effector macrophage phenotype that mediates accelerated helminth expulsion

Nature Immunology volume 15, pages 938946 (2014) | Download Citation

Abstract

We examined the role of innate cells in acquired resistance to the natural murine parasitic nematode, Nippostrongylus brasiliensis. Macrophages obtained from lungs as late as 45 d after N. brasiliensis inoculation were able to transfer accelerated parasite clearance to naive recipients. Primed macrophages adhered to larvae in vitro and triggered increased mortality of parasites. Neutrophil depletion in primed mice abrogated the protective effects of transferred macrophages and inhibited their in vitro binding to larvae. Neutrophils in parasite-infected mice showed a distinct transcriptional profile and promoted alternatively activated M2 macrophage polarization through secretory factors including IL-13. Differentially activated neutrophils in the context of a type 2 immune response therefore prime a long-lived effector macrophage phenotype that directly mediates rapid nematode damage and clearance.

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Acknowledgements

Mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the US Department of Agriculture (USDA). The USDA is an equal opportunity provider and employer. Supported by National Institutes of Health (1R01AI107588 to W.C.G. and C.C.K.; 5R01AI031678 to W.C.G.; R00AI085035 to C.C.K.) and the Agricultural Research Service of the USDA (1235-51000-058 to J.F.U. Jr.).

Author information

Affiliations

  1. Center for Immunity and Inflammation, New Jersey Medical School, Rutgers—The State University of New Jersey, Newark, New Jersey, USA.

    • Fei Chen
    • , Wenhui Wu
    • , Ariel Millman
    • , Nirav Patel
    •  & William C Gause
  2. Department of Medicine, New Jersey Medical School, Rutgers—The State University of New Jersey, Newark, New Jersey, USA.

    • Fei Chen
    • , Wenhui Wu
    • , Ariel Millman
    • , Nirav Patel
    •  & William C Gause
  3. Department of Medicine, Division of Experimental Medicine University of California, San Francisco, California, USA.

    • Joshua F Craft
    • , Eunice Chen
    •  & Charles C Kim
  4. Laboratoire de Chimie et Biochimie, Pharmacologiques et Toxicologiques, Paris, France.

    • Jean L Boucher
  5. Beltsville Human Nutrition Research Center, Diet, Genomics, and Immunology Laboratory, US Department of Agriculture, Agricultural Research Service, Beltsville, Maryland, USA.

    • Joseph F Urban Jr

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Contributions

W.C.G., F.C., C.C.K. and J.F.U. Jr. designed the experiments; F.C., W.W., A.M., J.F.C., E.C. and N.P. did the experiments; J.L.B. prepared and provided the BEC; and W.C.G., F.C., W.W. and C.C.K. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to William C Gause.

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https://doi.org/10.1038/ni.2984

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