Characterising the immune response following nasal colonisation of Staphylococcus aureus

Abstract

Staphylococcus aureus (S. aureus) is an opportunistic pathogen found in the nasal passage of 20%~30% of humans. Persistent nasal carriage of S. aureus is a significant risk factor for various diseases, including secondary bacterial pneumonia. To date, there is no vaccine available against S. aureus and the emergence of multidrug resistant strains limit the use of antibiotics as a treatment option. Little research has been undertaken to define the environmental, physiological and immunological changes that cause S. aureus to shift from the upper to the lower respiratory tract and convert from a commensal organism to pathogenic threat. In this project, we have established a nasal colonisation model of S. aureus in C57BL/6 mice and characterised the role of the innate and adaptive immune response in preventing the dissemination of S. aureus from the upper to the lower airways. Using this model, we have found that while both innate and adaptive immune responses are involved in the clearance of S. aureus from the nasal passage, only neutrophils play a critical role in keeping S. aureus confined to the nose and preventing spread into other organs. While the adaptive immune system does not play a role in preventing the spread of nasal S. aureus, it does play an important role bacterial clearance from this site. Moreover, immunisation with heat-killed S. aureus represents an effective approach to limit mice from being nasally colonised with S. aureus. Collectively our research demonstrates that both arms of the immune system can be harnessed to limit the colonisation and dissemination of S. aureus infection.