Staphylococcal Protein A Induces Leukocyte Necrosis by Complexing with Human Immunoglobulins
Proinnsias G. Fox, Francesca Schiavetti, Rino Rappuoli, Rachel M. McLoughlin, Fábio Bagnoli
Abstract
Staphylococcus aureus is one of the largest health care threats faced by humankind, with a reported mortality rate within the United States greater than that of HIV/AIDS, tuberculosis, and viral hepatitis combined. One of the defining features of S. aureus as a human pathogen is its ability to evade and impair the human immune response through expression of staphylococcal protein A. Herein, we show that SpA induces necrosis in various immune cells by complexing with human immunoglobulins. Vaccination of mice with a nontoxigenic SpA mutant induced sera capable of inhibiting this mechanism. These observations shed new light on the toxic mechanisms of this key staphylococcal virulence factor and on protective modalities of SpA-based vaccination.