Colonization by Superantigen Producing <i>Staphylococcus aureus</i> in Mice Enhances the Capacity to Develop Oral Tolerance

Microbial stimulation in early childhood may be necessary for proper maturation of the immunesystem. Infants colonized with Staphylococcus aureus have low risk of developing food allergy.Neonatal exposure to staphylococcal superantigen improves oral tolerance and enhances protectionin experimental allergy models. Here, we used three wild-type strains of S. aureus, naturallyharboring genes for different superantigens (SElM/SElO alone, or in combination with SEA orTSST-1). We first investigated their in vitro stimulatory capacity of splenocytes from germ-freemice. Secondly, germ-free mice were colonized with the strains and their capacity to develop oraltolerance was tested in a food allergy model. In vitro, S. aureus with only SElM/SElO genes promotedthe strongest B-cell stimulation. S. aureus carrying gene for SEA induced the highest proportionof CD4+FoxP3+ T cells. The proportion of regulatory T cells was inversely correlated toB-cell proliferation, indicating suppressive ability of these cells. All strains were equally able tocolonize the germ-free gut, initially achieving 1010CFU/g faeces, which decreased to 105 over a periodof six weeks. Mice colonized with S. aureus carrying genes for SEA or TSST-1 had improvedcapacity to develop tolerance compared to germ-free mice. These results suggest that colonizationby S. aureus producing superantigens may improve active tolerance to gut allergens.