Abstract
Staphylococcus aureus can lead to chronic infections and abscesses in internal organs including kidneys, which are associated with the expansion of myeloid-derived suppressor cells (MDSCs) and their suppressive effect on T cells. Here, we developed a mathematical model of chronic S.aureus infection that incorporates the T-cell suppression by MDSCs and suggests therapeutic strategies for S.aureus clearance. A therapeutic protocol with heat-killed S.aureus (HKSA) was quantified in silico and tested invivo. Contrary to the conventional administration of heat-killed bacteria as vaccination prior to infection, we administered HKSA as treatment in chronically infected hosts. Our treatment eliminated S.aureus in kidneys of all chronically S.aureus-infected mice, reduced MDSCs, and reversed T-cell dysfunction by inducing acute inflammation during ongoing, chronic infection. This study is a guideline for a treatment protocol against chronic S.aureus infection and renal abscesses by repurposing heat-killed treatments, directed by mathematical modeling.
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