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

Nat Immunol. 2014 Oct;15(10):938-46. doi: 10.1038/ni.2984. Epub 2014 Aug 31.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptive Immunity / immunology*
  • Animals
  • Cell Adhesion / immunology
  • Cell Adhesion / physiology
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / immunology
  • Cytokines / metabolism
  • Disease Resistance / immunology
  • Female
  • Flow Cytometry
  • Host-Parasite Interactions / immunology
  • Interleukin-13 / genetics
  • Interleukin-13 / immunology
  • Interleukin-13 / metabolism
  • Interleukin-4 Receptor alpha Subunit / genetics
  • Interleukin-4 Receptor alpha Subunit / immunology
  • Interleukin-4 Receptor alpha Subunit / metabolism
  • Larva / immunology
  • Larva / physiology
  • Lung / immunology
  • Lung / metabolism
  • Lung / parasitology
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Neutrophils / immunology*
  • Neutrophils / metabolism
  • Nippostrongylus / immunology*
  • Nippostrongylus / physiology
  • Oligonucleotide Array Sequence Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Strongylida Infections / genetics
  • Strongylida Infections / immunology*
  • Strongylida Infections / parasitology
  • Transcriptome / immunology

Substances

  • Cytokines
  • Interleukin-13
  • Interleukin-4 Receptor alpha Subunit

Associated data

  • GEO/GSE46437