IL-17 producing tissue-resident memory T-cells expanded during Staphylococcus aureus nasal colonisation provide heterologous immune protection.

Staphylococcus aureus persistently colonises the nasal tissue (NT) of a significant proportion of the population. The long-lasting impact that asymptomatic S. aureus exposure has on immune memory at colonised barrier sites is incompletely understood, potentially impacting vaccine responsiveness in a pre-exposed population. Tissue resident memory (TRM) cells are long-lived T-cells which remain poised at barrier sites for localised reactivation following antigen exposure. This study demonstrates an increase in NT CD4+ and {gamma}{delta}+ TRM cells in response to S. aureus colonisation, which undergo expansion and IL-17 production upon secondary S. aureus exposure. Interestingly, these cells were also capable of non-specific reactivation, with IL-17+ TRM cells in S. aureus colonised mice enhancing protection against K. pneumoniae infection. Ex-vivo data suggest that non-specific CD4+ TRM cell re-activation is pro-inflammatory cytokine dependent, but antigen independent. Overall, these findings demonstrate that S. aureus nasal colonisation shapes long-lasting TRM cell responses in the NT, which have the potential for non-specific bystander reactivation during subsequent heterologous infection.