Toxin-neutralizing Abs are associated with improved T cell function following recovery from Staphylococcus aureus infection

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Abstract

BACKGROUND T cell responses are impaired in Staphylococcus aureus–infected children, highlighting a potential mechanism of immune evasion. This study tested the hypotheses that toxin-specific antibodies protect immune cells from bacterial killing and are associated with improved T cell function following infection.METHODS S. aureus–infected and healthy children (N = 33 each) were prospectively enrolled. During acute infection and convalescence, we quantified toxin-specific IgG levels by ELISA, antibody function using a cell killing assay, and functional T cell responses by ELISPOT.RESULTS There were no differences in toxin-specific IgG levels or ability to neutralize toxin-mediated immune cell killing between healthy and acutely infected children, but antibody levels and function increased following infection. Similarly, T cell function, which was impaired during acute infection, improved following infection. However, the response to infection was highly variable; up to half of children did not have improved antibody or T cell function. Serum from children with higher α-hemolysin–specific IgG levels more strongly protected immune cells against toxin-mediated killing. Importantly, children whose serum more strongly protected against toxin-mediated killing also had stronger immune responses to infection, characterized by more elicited antibodies and greater improvement in T cell function following infection.CONCLUSION This study demonstrates that, despite T cell impairment during acute infection, S. aureus elicits toxin-neutralizing antibodies. Individual antibody responses and T cell recovery are variable. These findings also suggest that toxin-neutralizing antibodies protect antigen-presenting cells and T cells, thereby promoting immune recovery. Finally, failure to elicit toxin-neutralizing antibodies may identify children at risk for prolonged T cell suppression.FUNDING NIH National Institute of Allergy and Infectious Diseases R01AI125489 and Nationwide Children’s Hospital.

Authors

Maureen Kleinhenz, Zhaotao Li, Usha Chidella, Walissa Picard, Amber Wolfe, Jill Popelka, Robin Alexander, Christopher P. Montgomery