Extracellular vesicles from a helminth parasite suppress macrophage activation and constitute an effective vaccine for protective immunity
| Autor: | Jessica G. Borger, Elaine Robertson, Jana McCaskill, Henry J. McSorley, Rick M. Maizels, Yvonne Harcus, Amy H. Buck, Fabio Simbari, Gillian Coakley, Marissa Millar |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cytochalasin D Antibodies Helminth Bone Marrow Cells Article General Biochemistry Genetics and Molecular Biology Neutralization Microbiology Extracellular Vesicles Mice 03 medical and health sciences 0302 clinical medicine Immune system Downregulation and upregulation Animals Macrophage Parasites helminth lcsh:QH301-705.5 Nematospiroides dubius Vaccines biology Macrophages Immunity host-pathogen Receptors Interleukin Macrophage Activation vaccination biology.organism_classification Interleukin-1 Receptor-Like 1 Protein 3. Good health Vaccination 030104 developmental biology lcsh:Biology (General) macrophage alternative activation Antibody Formation biology.protein Tumor necrosis factor alpha extracellular vesicle Heligmosomoides polygyrus Antibody 030215 immunology |
| Zdroj: | Cell Reports, Vol 19, Iss 8, Pp 1545-1557 (2017) Cell Reports Coakley, G, McCaskill, J L, Borger, J G, Simbari, F, Robertson, E, Millar, M, Harcus, Y, McSorley, H J, Maizels, R M & Buck, A H 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 |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2017.05.001 |
| Popis: | Summary 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. Graphical Abstract Highlights • EVs from a nematode parasite suppress type 1 and type 2 activation of macrophages • Antibodies block EV function and increase their co-localization with the lysosome in macrophages • EV vaccination generates strong antibody responses and protective immunity against infection • EVs target both the IL-33 pathway and macrophage activation to counter parasite expulsion Coakley et al. find that extracellular vesicles (EVs) from a nematode parasite can suppress host macrophage activation and the alarmin receptor ST2 and that this can be blocked by antibodies. Vaccination with EVs drives strong antibody responses, conferring protection against infection. The authors thus highlight a role for EVs in parasite-host crosstalk. |
| Databáze: | OpenAIRE |
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