Enhancement of bacterial virulence by antibody neutralization of immune-activating toxins

Bacterial pathogens release a number of toxins that are able to form pores in target host cells, which can result in their destruction. Due to this property of this subgroup of toxins, they are considered virulence factors. A lesser known ability of these toxins when present at lower concentrations that are insufficient for host cell lysis to occur, is their activation of host immune cells. The Panton-Valentine Leukocidin (PVL) secreted by an alarming percentage of Staphylococcus aureus causing community-acquired infections, is one such: toxin. Due to the low inoculum of S. aureus we used to establish skin abscesses in a murine model of infection, lower amounts of PVL are likely to be present early in infection, hence, the proinflammatory properties of PVL may be more evident. Our data not only suggested that this was indeed the case, but we also showed that antibodies directed to PVL neutralized immune activation by this toxin resulting in a less robust host innate immune response. Thus, given the high levels of antibodies to PVL present in healthy individuals, these antibodies may directly enhance the virulence of PVL-producing S. aureus by dampening the innate immune response to infection. Since many pore-forming toxins share this dual property of concentration-dependent host cell lysis and immune activation, it is interesting to speculate that antibodies raised to some bacterial toxins may have the opposite intended outcome of directly enhancing bacterial virulence instead of controlling infection.