Pathogens as commensals: microbial priming of the immune system and heterologous protection

Exposure to microbes is essential to promote the development of the host's immune system. Commensal microbes (i.e. the microbiota) which are acquired early in life play a vital role in immune priming. Whilst many organisms within the microbiota are harmless, some can be considered opportunistic pathogens. Examples include <i>Staphylococcus aureus</i>, <i>Streptococcus pneumoniae</i> and <i>Pseudomonas aeruginosa</i>, and these organisms can also contribute to the development of a healthy host immune system. At the extreme end of the spectrum, pathogens which typically do not form part of the microbiota (e.g. <i>Mycobacterium tuberculosis</i>, <i>Bordetella pertussis</i> and <i>Salmonella</i> Typhimurium) have been shown to provide cross-protection against infectious and non-infectious diseases in mice. Attenuated strains of these pathogens, such as BPZE1, could have clinical applications, whilst Bacillus Calmette-Guérin, a live-attenuated <i>Mycobacterium bovis</i> strain, has been shown to have non-specific effects against cancers and other diseases. A wide range of organisms, from harmless microbiota to potentially life-threatening infections, interact with the host immune system and can prime or modulate the immune response in different ways. In this review, we discuss the important role that pathogens, including opportunistic components of the microbiota, play in the development and maintenance of host immunity to a wide range of infectious and non-infectious diseases.