MMR vaccination induces trained immunity via functional and metabolic reprogramming of γδ T cells
Rutger J. Röring, Priya A. Debisarun, Javier Botey-Bataller, Tsz Kin Suen, Özlem Bulut, Gizem Kılıç, Valerie A. C. M. Koeken, Andrei Sarlea, Harsh Bahrar, Helga Dijkstra, Heidi Lemmers, Katharina L. Gössling, Nadine Rüchel, Philipp Niklas Ostermann, Lisa Müller, Heiner Schaal, Ortwin Adams, Arndt Borkhardt, Yavuz Ariyürek, Emile J. de Meijer, Susan L. Kloet, Jaap ten Oever, Katarzyna Placek, Yang Li, Mihai G. Netea
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. Using single-cell RNA-Seq, we found that MMR caused transcriptomic changes in CD14+ 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 IFN-γ, 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.