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To celebrate Day of Immunology on 29 April 2020, we asked some of our scientists to summarise their research advances into the immune system. Each day this week we’ll be delving into a different area of this research. In today’s article we analyse the role of our microbiota in immunological memory.

Microbes, our microbiota, form just as much a part of our bodies as our own cells. In fact, the bacteria inside our body outnumber our own cells. Interactions with the microbiota influence many aspects of the immune system, including the development, specialisation and function of immune cells.

Killer T cells are the elite guard of the immune system that kill infected cells by targeting specific pathogens (i.e one may target a marker from an influenza virus while another might target a marker from the tuberculosis bacteria). After an infection, some remain behind as long-lived memory T cells, that quickly become licensed to kill should the same pathogen return, protecting us from re-infection. 

The University of Melbourne’s Dr Annabell Bachem and colleagues at the Doherty Institute revealed a role for the microbiota in promoting the long-term survival of memory T cells. Metabolites made by microbes appear to rewire the metabolism of activated killer T cells that enable them to transition into quiescent, memory T cells.  

The researchers found that germ-free mice, with no previous exposure to any microorganisms, and mice treated with antibiotics had impaired killer T cell responses upon infection. Additionally, these killer T cells failed to transition into memory cells afterwards to protect mice from reinfection.

The team realised that microbiota and the nutrients they make - fatty acids – promote the transition into memory T cells. The presence and uptake of these fatty acids rewire the cells to increase their metabolism and enter an energetic state to boost their defences upon reinfection. The formation of memory T cells are therefore based on metabolic changes in killer T cells in response to cues from microbes.

The interactions between microbes and the immune system have wide-ranging consequences for infection control. The findings of this study have important implications for vaccination and immunotherapy – not only do vaccines have to generate sufficient immune responses, their long-term effectiveness may depend on our microbiota and diets to ensure the durability of protective memory T cells.

A paper on this research was published in Immunity.