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

Neutrophils sense microbe size and selectively release neutrophil extracellular traps in response to large pathogens.

Author information

1
Division of Molecular Immunology, Medical Research Council National Institute for Medical Research, Mill Hill, London, UK.
2
Aberdeen Fungal Group, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, UK.
3
Division of Mycobacterial Research, Medical Research Council National Institute for Medical Research, Mill Hill, London, UK.

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.

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PMID:
25217981
PMCID:
PMC4236687
DOI:
10.1038/ni.2987
[Indexed for MEDLINE]
Free PMC Article

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