Staphylococcus aureus toxin suppresses antigen-specific T cell responses

Brandon Lee, Reuben Olaniyi, Jakub M. Kwiecinski, Juliane Bubeck Wardenburg

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Staphylococcus aureus remains a leading cause of human infection. These infections frequently recur when the skin is a primary site of infection, especially in infants and children. In contrast, invasive staphylococcal disease is less commonly associated with reinfection, suggesting that tissue-specific mechanisms govern the development of immunity. Knowledge of how S. aureus manipulates protective immunity has been hampered by a lack of antigen-specific models to interrogate the T cell response. Using a chicken egg OVA–expressing S. aureus strain to analyze OVA-specific T cell responses, we demonstrated that primary skin infection was associated with impaired development of T cell memory. Conversely, invasive infection induced antigen-specific memory and protected against reinfection. This defect in adaptive immunity following skin infection was associated with a loss of DCs, attributable to S. aureus α-toxin (Hla) expression. Gene- and immunization-based approaches to protect against Hla during skin infection restored the T cell response. Within the human population, exposure to α-toxin through skin infection may modulate the establishment of T cell–mediated immunity, adversely affecting long-term protection. These studies prompt consideration that vaccination targeting S. aureus may be most effective if delivered prior to initial contact with the organism.

Original languageEnglish
Pages (from-to)1122-1127
Number of pages6
JournalJournal of Clinical Investigation
Volume130
Issue number3
DOIs
StatePublished - Mar 2 2020

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