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

Nora Branzk, Aleksandra Lubojemska, Sarah E Hardison, Qian Wang, Maximiliano G Gutierrez, Gordon D Brown, Venizelos Papayannopoulos

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366 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1017-1025
Number of pages9
JournalNature Immunology
Volume15
Issue number11
Early online date14 Sep 2014
DOIs
Publication statusPublished - 14 Sep 2014

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    Branzk, N., Lubojemska, A., Hardison, S. E., Wang, Q., Gutierrez, M. G., Brown, G. D., & Papayannopoulos, V. (2014). Neutrophils sense microbe size and selectively release neutrophil extracellular traps in response to large pathogens. Nature Immunology, 15(11), 1017-1025. https://doi.org/10.1038/ni.2987