Hookworms evade host immunity by secreting a deoxyribonuclease to degrade neutrophil extracellular traps

Bouchery, Tiffany, Moyat, Mati, Sotillo, Javier, Silverstein, Solomon, Volpe, Beatrice, Coakley, Gillian, Tsourouktsoglou, Theodora-Dorita, Becker, Luke, Shah, Kathleen, Kulagin, Manuel, Guiet, Romain, Camberis, Mali, Schmidt, Alfonso, Seitz, Arne, Giacomin, Paul, Le Gros, Graham, Papayannopoulos, Venizelos, Loukas, Alex, and Harris, Nicola L. (2020) Hookworms evade host immunity by secreting a deoxyribonuclease to degrade neutrophil extracellular traps. Cell Host & Microbe, 27 (2). 277-289.e6.

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Abstract

Hookworms cause a major neglected tropical disease, occurring after larvae penetrate the host skin. Neutrophils are phagocytes that kill large pathogens by releasing neutrophil extracellular traps (NETs), but whether they target hookworms during skin infection is unknown. Using a murine hookworm, Nippostrongylus brasiliensis, we observed neutrophils being rapidly recruited and deploying NETs around skin-penetrating larvae. Neutrophils depletion or NET inhibition altered larvae behavior and enhanced the number of adult worms following murine infection. Nevertheless, larvae were able to mitigate the effect of NETs by secreting a deoxyribonuclease (NbDNase II) to degrade the DNA backbone. Critically, neutrophils were able to kill larvae in vitro, which was enhanced by neutralizing Nb-DNase II. Homologs of Nb-DNase II are present in other nematodes, including the human hookworm, Necator americanus, which also evaded NETs in vitro. These findings highlight the importance of neutrophils in hookworm infection and a potential conserved mechanism of immune evasion.

Item ID: 62485
Item Type: Article (Research - C1)
ISSN: 1934-6069
Copyright Information: Crown Copyright © 2020 Published by Elsevier Inc.
Funders: Swiss National Science Foundation (SNSF), Health Research Council of New Zealand (HRCNZ), Marjorie Barclay Trust, New Zealand, National Health and Medical Research Council (NHMRC) of Australia
Projects and Grants: SNSF SNF310030_156517, NHMRC SRF-B fellowship
Date Deposited: 11 Mar 2020 07:38
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320701 Medical bacteriology @ 50%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320704 Medical parasitology @ 50%
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