Examining the role of IgA in a persistent model of Staphylococcus aureus colonization

Staphylococcus aureus is a human-adapted pathogen that replicates by asymptomatically colonizing its host. Nasal colonization occurs in the first weeks of life and persists in about 30% of the population. Using the mouse-adapted strain WU1 to model persistent colonization, we reported earlier that inoculation of bacteria lacking Staphylococcal protein A (SpA/Δ spa ) or neutralization of SpA through vaccination result in the slow decolonization of animals. Secretory (S)IgA is considered a first line of defense against pathogens at mucosal surfaces. Here, we use Ighasec -/- mutant mice to evaluate the contribution of SIgA towards decolonization. We observe that WU1 burdens are reduced in colonized Ighasec -/- mice compared to C57BL/6J animals. Both C57BL/6J and Ighasec -/- mice eliminate Δ spa bacteria, yet elimination occurs more rapidly in animals lacking IgA. SpA captures Fab-V H 3-type antibodies, including IgA, on the bacterial cell surface. We propose that this activity promotes colonization. Yet, we also find that antibody responses to the pathogen are altered when SpA and IgA are missing. Colonized C57BL/6J mice display a low serum IgG2c/IgG1 ratio towards staphylococcal antigens. This ratio is increased in animals colonized with Δ spa and is further enhanced in Ighasec -/- mice. We attribute the former to the loss of immune evasion activity in absence of SpA, and the latter to a host compensatory mechanism upon exposure to S. aureus . Importantly, the increased IgG2c/IgG1 ratio correlates with decolonization and enhanced killing of S. aureus . Similarly, we observe that decolonization induced by SpA-vaccination is accelerated in Ighasec -/- mice which display higher anti-SpA IgG2c titers as compared to C57BL/6J animals. Together, these findings suggest that S. aureus exploits SIgA in a SpA-dependent manner for colonization and in absence of IgA, serum opsonizing antibodies may promote bacterial clearance at mucosal surfaces.