Staphylococcus aureus promotes strain-dependent immunopathology during cutaneous leishmaniasis through induction of...

Cutaneous leishmaniasis is a parasitic infection that causes a spectrum of pathology ranging from single, self-healing lesions to disfiguring chronic wounds. In severe disease, uncontrolled inflammation exacerbates tissue damage and delays healing, though the contributing factors are unclear. We previously observed that delayed healing was associated with Staphylococcus aureus in the lesional microbiota of patients with cutaneous leishmaniasis. To investigate how S. aureus impacts immunopathology during leishmania infection, we established a murine model of S. aureus colonization with clinical isolates followed by Leishmania infection. S. aureus triggered early production of interleukin (IL)-1β during Leishmania infection, which was critical for neutrophil recruitment and cutaneous inflammation. S. aureus isolates differentially induced IL-1β and neutrophil recruitment, and isolates that induced greater neutrophil recruitment were resistant to neutrophil killing and persisted longer. We reveal a mechanism whereby S. aureus mediates immunopathology during cutaneous leishmaniasis, suggesting IL-1β as a promising immunomodulatory target for non-healing infections.