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.

Immune memory was considered for decades an exclusive hallmark of the adaptive immune response. However, recent studies have revealed that innate immune cells can also ‘recall’ information of a primary insult during infection or vaccination and deploy robust antigen-agonistic immune reactivity upon secondary challenge. This de-facto innate immune memory response is designated as ‘trained immunity’. γδ T cells are unconventional T cells that possess unique immunologic features of both adaptive and innate immunity. Their immune memory responses to various bacterial and viral agents were originally described to be of an adaptive immune nature. Nevertheless, growing evidence shows that γδ T cells can also mount antigen-independent memory responses resembling trained immunity. In this review, we discuss the dual nature of immune memory responses of γδ T cells and provide insights into their important role in protection against bacterial, viral, and parasitic infections in humans and animals.

Over the last decade, the African turquoise killifish, Nothobranchius furzeri , has emerged as an important model system for the study of vertebrate biology and ageing. However, rearing this fish in captivity can pose challenges, due to the short window of fertility, inbreeding problems, and the continuous maintenance of different strains and transgenic lines. To date, the main means of long term strain maintenance is to arrest embryos in diapause, a poorly understood and unreliable method. To solve these problems, we developed a robust protocol to cryopreserve sperm and to revive them for in vitro fertilization (IVF), as a better option for long term storage of N. furzeri lines. We tested a variety of extender and activator buffers for sperm in vitro fertilization, as well as cryoprotectants to achieve maximal long term storage and fertilization conditions tailored to this species. Our optimized protocol was able to preserve sperm in a cryogenic condition for months and to revive an average of 40% upon thawing. Thawed sperm were able to fertilize nearly the same number of eggs as natural fertilization, with an average of ~25% and peaks of ~55% fertilization. This technical advance will greatly facilitate the use of N. furzeri as a model organism.