Hookworms Evade Host Immunity by Secreting a Deoxyribonuclease to Degrade Neutrophil Extracellular Traps

Tiffany Bouchery, Mati Moyat, Javier Sotillo, Solomon Silverstein, Beatrice Volpe, Gillian Coakley, Theodora-Dorita Tsourouktsoglou, Luke Becker, Kathleen Shah, Manuel Kulagin, Romain Guiet, Mali Camberis, Alfonso Schmidt, Arne Seitz, Paul Giacomin, Graham Le Gros, Venizelos Papayannopoulos, Alex Loukas, Nicola L. Harris

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

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 (Nb-DNase 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.

Original languageEnglish
Pages (from-to)277-289.e6
Number of pages19
JournalCell Host and Microbe
Volume27
Issue number2
DOIs
Publication statusPublished - 12 Feb 2020

Keywords

  • DNAse II
  • helminth
  • hookworm
  • immune-evasion
  • neutrophil extracellular traps
  • neutrophils
  • Nippostrongylus brasiliensis

Cite this

Bouchery, T., Moyat, M., Sotillo, J., Silverstein, S., Volpe, B., Coakley, G., Tsourouktsoglou, T-D., Becker, L., Shah, K., Kulagin, M., Guiet, R., Camberis, M., Schmidt, A., Seitz, A., Giacomin, P., Le Gros, G., Papayannopoulos, V., Loukas, A., & Harris, N. L. (2020). Hookworms Evade Host Immunity by Secreting a Deoxyribonuclease to Degrade Neutrophil Extracellular Traps. Cell Host and Microbe, 27(2), 277-289.e6. https://doi.org/10.1016/j.chom.2020.01.011