Staphylococcus aureus promotes strain-dependent immunopathology during cutaneous leishmaniasis through induction of IL-1beta
Cutaneous leishmaniasis is a parasitic infection that causes a spectrum of pathology ranging from single, self-healing lesions to disfiguring chronic wounds. In severe forms of disease, uncontrolled inflammation exacerbates tissue damage and delays healing, though the contributing factors are unclear. We previously identified an association between delayed healing and Staphylococcus aureus in the lesional microbiota of patients. To investigate the role of S. aureus in regulating immunopathology and lesion healing, we established a murine leishmania-S. aureus co-infection model and a collection of cultured isolates from patient lesions. S. aureus triggered early production of IL-1beta during leishmania infection, which was critical for neutrophil recruitment and cutaneous inflammation. Morphologically and phylogenetically distinct strains differentially induced IL-1beta and recruited neutrophils. Strains that induced greater neutrophil recruitment were resistant to neutrophil killing and persisted longer in the lesion. We reveal a mechanism whereby S. aureus mediates immunopathology and healing responses in cutaneous leishmania in a strain-dependent manner, suggesting IL-1beta as a promising immunomodulatory target for non-healing infections.Overall design: bulk RNA-seq from mouse ears infected with L. major and colonized with S. aureus at day 7 post-infection