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MMR vaccination induces trained immunity via functional and metabolic reprogramming of γδ T cells.

The Journal of clinical investigation

Authors: Rutger J Röring, Priya A Debisarun, Javier Botey-Bataller, Tsz Kin Suen, Ozlem Bulut, Gizem Kilic, Valerie Acm Koeken, Andrei Sarlea, Harsh Bahrar, Helga Dijkstra, Heidi Lemmers, Katharina L Gössling, Nadine Rüchel, Philipp N Ostermann, Lisa Müller, Heiner Schaal, Ortwin Adams, Arndt Borkhardt, Yavuz Ariyurek, Emile J de Meijer, Susan L Kloet, Jaap Ten Oever, Katarzyna Placek, Yang Li, Mihai G Netea

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 γδ T cells. Monocyte function was not altered by MMR vaccination. In contrast, the function of γδ T cells was markedly enhanced by MMR vaccination, with higher production of TNF and IFNγ, as well as upregulation of cellular metabolic pathways. In conclusion, we describe a trained immunity program characterized by modulation of γδ T cell function induced by MMR vaccination.

PMID: 38290093

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