Neutrophils Sense Microbe Size and Selectively Release Neutrophil Extracellular Traps in Response to Large Pathogens

Nat Immunol. 2014 Nov;15(11):1017-25. doi: 10.1038/ni.2987. Epub 2014 Sep 14.

Abstract

Neutrophils are critical for antifungal defense, but the mechanisms that clear hyphae and other pathogens that are too large to be phagocytosed remain unknown. We found that neutrophils sensed microbe size and selectively released neutrophil extracellular traps (NETs) in response to large pathogens, such as Candida albicans hyphae and extracellular aggregates of Mycobacterium bovis, but not in response to small yeast or single bacteria. NETs were fundamental in countering large pathogens in vivo. Phagocytosis via dectin-1 acted as a sensor of microbe size and prevented NET release by downregulating the translocation of neutrophil elastase (NE) to the nucleus. Dectin-1 deficiency led to aberrant NET release and NET-mediated tissue damage during infection. Size-tailored neutrophil responses cleared large microbes and minimized pathology when microbes were small enough to be phagocytosed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / immunology
  • Aspergillus fumigatus / immunology
  • Candida albicans / immunology
  • Escherichia coli / immunology
  • Extracellular Traps / immunology*
  • Humans
  • Hyphae / immunology
  • Klebsiella pneumoniae / immunology
  • Lectins, C-Type / genetics
  • Lectins, C-Type / immunology*
  • Leukocyte Elastase / metabolism
  • Mycobacterium bovis / immunology
  • Neutrophil Activation / immunology*
  • Neutrophils / immunology*
  • Neutrophils / microbiology*
  • Phagocytosis / immunology*

Substances

  • CLEC7A protein, human
  • Lectins, C-Type
  • Leukocyte Elastase