Zhaotao Li1, Pavani Beesetty1,2, George Gerges1,3, Maureen Kleinhenz1, Melissa Moore-Clingenpeel4, Ching Yang1,5, Luul B Ahmed1,6, Josey Hensley7, Lisa Steele7, Anita S Chong8, Christopher P Montgomery1,7,9. 1. Center for Microbial Pathogenesis, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, Ohio, USA. 2. Present affiliation: Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada. 3. Present affiliation: College of Medicine, The Ohio State University, Columbus, OH, USA. 4. Biostatistics Resource, Nationwide Children's Hospital, Columbus, Ohio, USA. 5. Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA. 6. Present affiliation: College of Public Health, The Ohio State University, Columbus OH, USA. 7. Division of Critical Care Medicine, Nationwide Children's Hospital, Columbus, Ohio, USA. 8. Department of Surgery, University of Chicago, Chicago, Illinois, USA. 9. Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Abstract
BACKGROUND: Staphylococcus aureus infections are common throughout the lifespan, with recurrent infections occurring in nearly half of infected children. There is no licensed vaccine, underscoring the need to better understand how S. aureus evades protective immunity. Despite much study, the relative contributions of antibodies and T cells to protection against S. aureus infections in humans are not fully understood. METHODS: We prospectively quantified S. aureus-specific antibody levels by ELISA and T-cell responses by ELISpot in S. aureus-infected and healthy children. RESULTS: S. aureus-specific antibody levels and T-cell responses increased with age in healthy children, suggesting a coordinated development of anti-staphylococcal immunity. Antibody levels against leukotoxin E (LukE) and Panton-Valentine leukocidin (LukS-PV), but not α-hemolysin (Hla), were higher in younger infected children, compared with healthy children; these differences disappeared in older children. We observed a striking impairment of global and S. aureus-specific T-cell function in children with invasive and noninvasive infection, suggesting that S. aureus-specific immune responses are dysregulated during childhood infection regardless of the infection phenotype. CONCLUSIONS: These findings identify a potential mechanism by which S. aureus infection actively evades adaptive immune responses, thereby preventing the development of protective immunity and maintaining susceptibility to recurrent infection.
BACKGROUND: Staphylococcus aureus infections are common throughout the lifespan, with recurrent infections occurring in nearly half of infected children. There is no licensed vaccine, underscoring the need to better understand how S. aureus evades protective immunity. Despite much study, the relative contributions of antibodies and T cells to protection against S. aureus infections in humans are not fully understood. METHODS: We prospectively quantified S. aureus-specific antibody levels by ELISA and T-cell responses by ELISpot in S. aureus-infected and healthy children. RESULTS: S. aureus-specific antibody levels and T-cell responses increased with age in healthy children, suggesting a coordinated development of anti-staphylococcal immunity. Antibody levels against leukotoxin E (LukE) and Panton-Valentine leukocidin (LukS-PV), but not α-hemolysin (Hla), were higher in younger infected children, compared with healthy children; these differences disappeared in older children. We observed a striking impairment of global and S. aureus-specific T-cell function in children with invasive and noninvasive infection, suggesting that S. aureus-specific immune responses are dysregulated during childhood infection regardless of the infection phenotype. CONCLUSIONS: These findings identify a potential mechanism by which S. aureus infection actively evades adaptive immune responses, thereby preventing the development of protective immunity and maintaining susceptibility to recurrent infection.
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