TY - JOUR
T1 - Staphylococcus aureus toxin suppresses antigen-specific T cell responses
AU - Lee, Brandon
AU - Olaniyi, Reuben
AU - Kwiecinski, Jakub M.
AU - Wardenburg, Juliane Bubeck
N1 - Funding Information:
This work was supported by NIH grant AI097434 and a Burroughs Wellcome Foundation Investigators in the Pathogenesis of Infectious Disease Fellowship (to JBW). BL was supported by the University of Chicago Growth, Development, and Disabilities Training Program and NIH grant T32 HD007009.
Publisher Copyright:
© 2020, American Society for Clinical Investigation.
PY - 2020/3/2
Y1 - 2020/3/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85081120350&partnerID=8YFLogxK
U2 - 10.1172/JCI130728
DO - 10.1172/JCI130728
M3 - Article
C2 - 31873074
AN - SCOPUS:85081120350
SN - 0021-9738
VL - 130
SP - 1122
EP - 1127
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 3
ER -