This lecture explores how parasite-derived extracellular vesicles (EVs) shape host immunity and promote long-term infection. Using infection models, we investigate how these nanoscale messengers suppress inflammation and inspire new therapeutic strategies.

Helminths have coexisted with humans and animals for millennia, often establishing infections that persist for years without killing their host. Such chronicity suggests active immune calibration rather than simple immune evasion.

We explore the hypothesis that EVs released by parasitic worms modulate host immunity to favour coexistence.

Using infection models, transcriptomics, and human immune cell assays, we show that parasites EVs dampen inflammation in vitro and in vivo.

These findings suggest that parasites promote long-term survival by promoting a tolerogenic immune environment, and that their EVs may serve as biologically inspired nanotherapeutics for inflammatory disease.

EVs are natural nanoscale delivery systems transferring bioactive molecules between cells. Studying pathogen-derived EVs may inform the development of next-generation anti-inflammatory nanotherapeutics.

References

Midttun, H.L.E., Acevedo, N., Skallerup, P., Almeida, S., Skovgaard, K., Andresen, L., Skov, S., Caraballo, L., van Die, I., Jørgensen, C.B., Fredholm, M., Thamsborg, S.M., Nejsum, P.,* Williams, A.R.* (2018). Ascaris suum infection down-regulates mucosal inflammatory pathways in pigs in vivo and in human dendritic cells in vitro. Journal of Infectious Diseases, 218: 310-319

Hansen E.P., Fromm, B., Andersen, S.D., Marcilla, A., Andersen, K.L., Borup, A., Williams, A.R., Jex, A., Gasser, R.B., Young, N.D., Hall, R.S., Stensballe, A., Ovchinnikov, V., Yan, Y., Fredholm, M., Thamsborg, S.M., Nejsum, P. (2019). Exploration of extracellular vesicles from Ascaris suum provides evidence of parasite-host cross talk. Journal of Extracellular Vesicles, 8:1578116

Borup, A., Boysen, A.T., Ridolfi, A., Brucale, M., Valle, F., Paolini, L., Bergese, P., Nejsum, P. (2022). Comparison of separation methods for immunomodulatory extracellular vesicles from helminths. Journal of Extracellular Biology, 1:e41

Borup, A., Sharifpour, M.F., Rossen, L.S., Whitehead, B., Boysen, A.T., Olesen, R., Bohn, A.B., Ridolfi, A., Brucale, M., Valle, F., Paolini, L., Radeghieri, A., Bergese, P., Miles, K., Veitch, M., Thomas, T., Ruscher, R., Wangchuk, P., Giacomin, P., Loukas, A., Nejsum, P. (2025). Helminth extracellular vesicles co-opt host monocytes to drive T cell anergy. Journal of Extracellular Vesicles. 14:e70027