Extracellular Vesicles from a Helminth Parasite Suppress Macrophage Activation and Constitute an Effective Vaccine for Protective Immunity

Gillian Coakley, Jana L. McCaskill, Jessica G. Borger, Fabio Simbari, Elaine Robertson, Marissa Millar, Yvonne Harcus, Henry J. McSorley, Rick M. Maizels, Amy H. Buck

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Recent studies have demonstrated that many parasites release extracellular vesicles (EVs), yet little is known about the specific interactions of EVs with immune cells or their functions during infection. We show that EVs secreted by the gastrointestinal nematode Heligmosomoides polygyrus are internalized by macrophages and modulate their activation. EV internalization causes downregulation of type 1 and type 2 immune-response-associated molecules (IL-6 and TNF, and Ym1 and RELMα) and inhibits expression of the IL-33 receptor subunit ST2. Co-incubation with EV antibodies abrogated suppression of alternative activation and was associated with increased co-localization of the EVs with lysosomes. Furthermore, mice vaccinated with EV-alum generated protective immunity against larval challenge, highlighting an important role in vivo. In contrast, ST2-deficient mice are highly susceptible to infection, and they are unable to clear parasites following EV vaccination. Hence, macrophage activation and the IL-33 pathway are targeted by H. polygyrus EVs, while neutralization of EV function facilitates parasite expulsion.

Original languageEnglish
Pages (from-to)1545-1557
Number of pages13
JournalCell Reports
Volume19
Issue number8
DOIs
Publication statusPublished - 23 May 2017

Keywords

  • extracellular vesicle
  • helminth
  • host-pathogen
  • macrophage alternative activation
  • vaccination

Cite this

Coakley, Gillian ; McCaskill, Jana L. ; Borger, Jessica G. ; Simbari, Fabio ; Robertson, Elaine ; Millar, Marissa ; Harcus, Yvonne ; McSorley, Henry J. ; Maizels, Rick M. ; Buck, Amy H. / Extracellular Vesicles from a Helminth Parasite Suppress Macrophage Activation and Constitute an Effective Vaccine for Protective Immunity. In: Cell Reports. 2017 ; Vol. 19, No. 8. pp. 1545-1557.
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abstract = "Recent studies have demonstrated that many parasites release extracellular vesicles (EVs), yet little is known about the specific interactions of EVs with immune cells or their functions during infection. We show that EVs secreted by the gastrointestinal nematode Heligmosomoides polygyrus are internalized by macrophages and modulate their activation. EV internalization causes downregulation of type 1 and type 2 immune-response-associated molecules (IL-6 and TNF, and Ym1 and RELMα) and inhibits expression of the IL-33 receptor subunit ST2. Co-incubation with EV antibodies abrogated suppression of alternative activation and was associated with increased co-localization of the EVs with lysosomes. Furthermore, mice vaccinated with EV-alum generated protective immunity against larval challenge, highlighting an important role in vivo. In contrast, ST2-deficient mice are highly susceptible to infection, and they are unable to clear parasites following EV vaccination. Hence, macrophage activation and the IL-33 pathway are targeted by H. polygyrus EVs, while neutralization of EV function facilitates parasite expulsion.",
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Coakley, G, McCaskill, JL, Borger, JG, Simbari, F, Robertson, E, Millar, M, Harcus, Y, McSorley, HJ, Maizels, RM & Buck, AH 2017, 'Extracellular Vesicles from a Helminth Parasite Suppress Macrophage Activation and Constitute an Effective Vaccine for Protective Immunity' Cell Reports, vol. 19, no. 8, pp. 1545-1557. https://doi.org/10.1016/j.celrep.2017.05.001

Extracellular Vesicles from a Helminth Parasite Suppress Macrophage Activation and Constitute an Effective Vaccine for Protective Immunity. / Coakley, Gillian; McCaskill, Jana L.; Borger, Jessica G.; Simbari, Fabio; Robertson, Elaine; Millar, Marissa; Harcus, Yvonne; McSorley, Henry J.; Maizels, Rick M.; Buck, Amy H.

In: Cell Reports, Vol. 19, No. 8, 23.05.2017, p. 1545-1557.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Coakley, Gillian

AU - McCaskill, Jana L.

AU - Borger, Jessica G.

AU - Simbari, Fabio

AU - Robertson, Elaine

AU - Millar, Marissa

AU - Harcus, Yvonne

AU - McSorley, Henry J.

AU - Maizels, Rick M.

AU - Buck, Amy H.

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AB - Recent studies have demonstrated that many parasites release extracellular vesicles (EVs), yet little is known about the specific interactions of EVs with immune cells or their functions during infection. We show that EVs secreted by the gastrointestinal nematode Heligmosomoides polygyrus are internalized by macrophages and modulate their activation. EV internalization causes downregulation of type 1 and type 2 immune-response-associated molecules (IL-6 and TNF, and Ym1 and RELMα) and inhibits expression of the IL-33 receptor subunit ST2. Co-incubation with EV antibodies abrogated suppression of alternative activation and was associated with increased co-localization of the EVs with lysosomes. Furthermore, mice vaccinated with EV-alum generated protective immunity against larval challenge, highlighting an important role in vivo. In contrast, ST2-deficient mice are highly susceptible to infection, and they are unable to clear parasites following EV vaccination. Hence, macrophage activation and the IL-33 pathway are targeted by H. polygyrus EVs, while neutralization of EV function facilitates parasite expulsion.

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