Targeting lung-resident memory T cells via mucosal vaccination to combat staphylococcus aureus infections

Abstract

Staphylococcus aureus (S. aureus) pneumonia accounts for about 5% of community-acquired pneumonia and 10%-30% of hospital-acquired pneumonia, with high morbidity and mortality. Our group developed Recombinant five-antigen Staphylococcus aureus vaccine (rFSAV), and Phase III clinical trial (CTR20221329) used to prevent S. aureus infection after orthopedic surgery is under way. However, the protective effect on bacterial infection of mucosal tissue is not clear. In present study, rFSAV immunization via mucosal route can protect against pulmonary infection of different S. aureus strains and induce humoral and cellular immune responses, but the protective effect of rFSAV mucosal immunity does not necessarily depend on rFSAV specific antibodies. Through single-cell T-cell receptor (TCR) sequencing, it was discovered that there exists a highly expanded clone (HEC) in the immunized mice. Moreover, lung IL-17A + CD4 TRM cells could protect the mice from bacterial infection independent of circulating memory T cells, and could persist in the lung tissue of mice for a long time. Pulmonary IL-17A + CD4 TRM cells may rapidly recruit neutrophils to the lungs through IL-17A signaling pathway to enhance the mucosal immune protective effect of rFSAV. Thus, A deeper understanding of how the IL-17A + CD4 TRM that produce these cytokines could be selectively boosted or recalled can augment cellular immunity against S. aureus.