MMR vaccination induces a trained immunity program characterized by functional and metabolic reprogramming of γδ T cells

Roring, R. J.; Debisarun, P. A.; Botey-Bataller, J.; Suen, K. T.; Bulut, O.; Kilic, G.; Koeken, V. A. C. M.; Sarlea, A.; Bahrar, H.; Dijkstra, H.; Lemmers, H.; Goessling, K. L.; Ruechel, N.; Ostermann, P. N.; Mueller, L.; Schaal, H.; Adams, O.; Borkhardt, A.; Ariyurek, Y.; de Meijer, E. J.; Kloet, S.; ten Oever, J.; Placek, K.; Li, Y.; Netea, M. G.

doi:10.1101/2022.11.24.516894

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bioRxiv · 10.1101/2022.11.24.516894

MMR vaccination induces a trained immunity program characterized by functional and metabolic reprogramming of γδ T cells

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Abstract

The measles, mumps and rubella (MMR) vaccine protects against all-cause mortality in children, but the immunological mechanisms mediating these effects are poorly known. We systematically investigated whether MMR can induce long-term functional changes in innate immune cells, a process termed trained immunity, that could at least partially mediate this heterologous protection. In a randomized placebo-controlled trial, 39 healthy adults received either the MMR vaccine or a placebo. By using single-cell RNA-sequencing, we found that MMR caused transcriptomic changes in CD14-positive monocytes and NK cells, but most profoundly in {gamma}{delta} T cells. Surprisingly, monocyte function was not altered by MMR vaccination. In contrast, the function of {gamma}{delta} T cells was significantly enhanced by MMR vaccination, with higher production of TNF and IFN{gamma}, as well as upregulation of cellular metabolic pathways. In conclusion, we describe a new trained immunity program characterized by modulation of {gamma}{delta} T cell function induced by MMR vaccination. One-sentence summaryMMR vaccination induces cellular and metabolic reprogramming in {gamma}{delta} T cells towards a more active phenotype.

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Roring, R. J., Debisarun, P. A., Botey-Bataller, J., Suen, K. T., Bulut, O., Kilic, G., Koeken, V. A. C. M., Sarlea, A., Bahrar, H., Dijkstra, H., Lemmers, H., Goessling, K. L., Ruechel, N., Ostermann, P. N., Mueller, L., Schaal, H., Adams, O., Borkhardt, A., Ariyurek, Y., de Meijer, E. J., Kloet, S., ten Oever, J., Placek, K., Li, Y., Netea, M. G.. 2022-11-25. MMR vaccination induces a trained immunity program characterized by functional and metabolic reprogramming of γδ T cells. https://doi.org/10.1101/2022.11.24.516894

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