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

doi:10.1016/j.chom.2020.01.011

. 2020 Feb 12;27(2):277-289.e6.

doi: 10.1016/j.chom.2020.01.011.

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

Tiffany Bouchery¹, Mati Moyat¹, Javier Sotillo², Solomon Silverstein³, Beatrice Volpe⁴, Gillian Coakley³, Theodora-Dorita Tsourouktsoglou⁵, Luke Becker⁶, Kathleen Shah⁴, Manuel Kulagin⁴, Romain Guiet⁷, Mali Camberis⁸, Alfonso Schmidt⁹, Arne Seitz⁷, Paul Giacomin⁶, Graham Le Gros⁸, Venizelos Papayannopoulos⁵, Alex Loukas⁶, Nicola L Harris¹⁰

Affiliations

¹ Laboratory of Intestinal Immunology, Department of Immunology and Pathology, Monash University, Melbourne, VIC 3004, Australia; Laboratory of Intestinal Immunology, SV, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne CH-1015 Switzerland.
² Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4814, Australia; Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid 28222, Spain.
³ Laboratory of Intestinal Immunology, Department of Immunology and Pathology, Monash University, Melbourne, VIC 3004, Australia.
⁴ Laboratory of Intestinal Immunology, SV, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne CH-1015 Switzerland.
⁵ Antimicrobial Defense Laboratory, The Francis Crick Institute, 1 Midland Rd, London NW1 1AT, UK.
⁶ Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4814, Australia.
⁷ Bioimaging and Optics Core Facility, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne CH-1015, Switzerland.
⁸ Malaghan Institute of Medical Research, Wellington 6242, New Zealand.
⁹ Hugh Green Cytometry Centre, Malaghan Institute of Medical Research, Wellington 6242, New Zealand.
¹⁰ Laboratory of Intestinal Immunology, Department of Immunology and Pathology, Monash University, Melbourne, VIC 3004, Australia. Electronic address: nicola.harris@monash.edu.

PMID: 32053791
DOI: 10.1016/j.chom.2020.01.011

Free article

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

Tiffany Bouchery et al. Cell Host Microbe. 2020.

Free article

. 2020 Feb 12;27(2):277-289.e6.

doi: 10.1016/j.chom.2020.01.011.

Authors

Affiliations

¹ Laboratory of Intestinal Immunology, Department of Immunology and Pathology, Monash University, Melbourne, VIC 3004, Australia; Laboratory of Intestinal Immunology, SV, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne CH-1015 Switzerland.
² Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4814, Australia; Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid 28222, Spain.
³ Laboratory of Intestinal Immunology, Department of Immunology and Pathology, Monash University, Melbourne, VIC 3004, Australia.
⁴ Laboratory of Intestinal Immunology, SV, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne CH-1015 Switzerland.
⁵ Antimicrobial Defense Laboratory, The Francis Crick Institute, 1 Midland Rd, London NW1 1AT, UK.
⁶ Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4814, Australia.
⁷ Bioimaging and Optics Core Facility, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne CH-1015, Switzerland.
⁸ Malaghan Institute of Medical Research, Wellington 6242, New Zealand.
⁹ Hugh Green Cytometry Centre, Malaghan Institute of Medical Research, Wellington 6242, New Zealand.
¹⁰ Laboratory of Intestinal Immunology, Department of Immunology and Pathology, Monash University, Melbourne, VIC 3004, Australia. Electronic address: nicola.harris@monash.edu.

PMID: 32053791
DOI: 10.1016/j.chom.2020.01.011

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.

Keywords: DNAse II; Nippostrongylus brasiliensis; helminth; hookworm; immune-evasion; neutrophil extracellular traps; neutrophils.

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Conflict of interest statement

Declaration of Interests A.L. and P.G. are shareholders in Paragen Bio Pty Ltd, a biotechnology company focusing on the use of hookworm proteins to treat inflammation.

Comment in

The NET Effect of Neutrophils during Helminth Infection.
El-Naccache DW, Chen F, Chen N, Gause WC. El-Naccache DW, et al. Cell Host Microbe. 2020 Feb 12;27(2):165-168. doi: 10.1016/j.chom.2020.01.013. Cell Host Microbe. 2020. PMID: 32053785 Free PMC article.

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

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

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