Extracellular vesicles from a helminth parasite suppress macrophage activation and constitute an effective vaccine for protective immunity

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.