Extracellular Vesicles from a Helminth Parasite Suppress Macrophage Activation and Constitute an Effective Vaccine for Protective Immunity
作者： Gillian Coakley , Jana L. McCaskill , Jessica G. Borger , Fabio Simbari , Elaine Robertson
DOI: 10.1016/J.CELREP.2017.05.001
关键词: Microbiology 、 Heligmosomoides polygyrus 、 Immune system 、 Antibody 、 Vaccination 、 Downregulation and upregulation 、 Tumor necrosis factor alpha 、 Extracellular vesicle 、 Biology 、 Macrophage
摘要: 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 secreted by gastrointestinal nematode Heligmosomoides polygyrus are internalized macrophages and modulate activation. EV internalization causes downregulation type 1 2 immune-response-associated molecules (IL-6 TNF, Ym1 RELMα) inhibits expression IL-33 receptor subunit ST2. Co-incubation EV antibodies abrogated suppression alternative activation was associated increased co-localization lysosomes. Furthermore, mice vaccinated EV-alum generated protective immunity against larval challenge, highlighting an important role in vivo. In contrast, ST2-deficient highly susceptible to infection, they unable clear following vaccination. Hence, macrophage pathway targeted H. polygyrus EVs, while neutralization function facilitates parasite expulsion.
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