Lung Innate Immunity and Microbiome After Tuberculosis Exposure

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Tuberculosis (TB) kills more people than any other single infectious disease. It is estimated that 1 in 4 people are infected with the bug that causes TB. We really need an effective vaccine to prevent people getting TB, but we don't understand what sort of immune response is needed to protect people. The very early response to infection, called the innate immune response, is not well understood in TB, partly because it is difficult to study, as most of the changes happen before people get symptoms. In a recent study we have seen that human infection with BCG, a bacteria similar to the one that causes TB, results in significant changes in the early immune response in the lungs, which are not seen in the blood. The immune system is constantly coming into contact with different bacteria which live on the surfaces of our bodies, called the microbiome, this includes the linings of the airways (the tubes of the lungs). Understanding the interactions between the microbiome in the airways and immune system can help us to understand why some people can resist developing TB. This study has been designed to help to answer two key questions about the early immune responses to TB: 1. What is the early immune response to TB, and how does it vary between people? We will use samples of sputum from people who have recently been living with someone with an active TB infection. We will measure the type of immune cells present in these samples and how they change over time, comparing what we find with blood results. This will help us to build a picture of what is happening both in the airways and in the blood during the early immune responses to TB. The immune response to TB is also different in different people. Importantly, some people never develop a memory (or 'adaptive') immune response. This may suggest that the early immune response is able to clear all of the infection quickly in these people. Understanding differences in the early immune response would give us ways to develop more effective vaccines and treatments. 2. Does the microbiome of the airway help in protecting people from TB? The bacteria of the microbiome live in unison with our cells, and are able to survive without causing an infection which makes us unwell. It has increasingly been understood that these bacteria help to "train" our immune system to work better. We will look at which bacteria are living normally in the airways of the people recruited to our study, and see how these bacteria change over time. This will help us to get a greater understanding of how the immune system and the microbiome work together, and if there is a role for the microbiome in preventing TB infections. In summary this study will look at the early immune responses and the airway microbiome of people who have recently come into contact with the bacteria which causes TB. The differences that we identify could help us explain why some people have protection from TB, and provide us with novel approaches to developing new ways to protect others.