Environmentally exposed surfaces in humans are colonized by a vast number of foreign microbes (the commensal microbiota) and these organisms play a key role in regulating mucosal and systemic immune function. Disruption of this relationship is linked to a wide variety of diseases and immune dysfunctions, including chronic inflammatory conditions at the mucosa, autoimmunity and increased susceptibility to infection by bacteria, viruses and parasites. There remains, however, a major gap in understanding the mechanistic basis for the influence of the commensal microbiota on immune function, especially systemic immunity. The broad theme of my research, therefore, is to understand how programming of innate immunity by the microbiota influences host responses to bacterial infection and vaccination, and how changes to the composition of the microbiota disrupts these responses.