Tissue-specific patterning of host innate immune responses by Staphylococcus aureus α-toxin.

摘要: Immunomodulatory cytotoxins are prominent virulence factors produced by Staphylococcus aureus, a leading cause of bacterial sepsis, skin infection, and pneumonia. S. aureus α-toxin is pore-forming toxin that utilizes widely expressed receptor, ADAM10, to injure the host epithelium, endothelium, immune cells. As each tissue characterized unique composition resident cells recruited cells, outcome α-toxin-mediated injury may depend on infected environment. Utilizing myeloid lineage-specific Adam10 knockout mice, we show exerts tissue-specific effects innate immunity staphylococcal infection. Loss ADAM10 expression exacerbates yet affords protection against lethal These diverse outcomes not related altered cell recruitment, but rather correlate with defect in toxin-induced IL-1β production. Extension these studies through analysis double-knockout mice affecting both lineage either or lung epithelium highlight prominence governing Together, provide evidence specificity cytotoxin action modulation immunity, illustrate infection collective manifestation all within microenvironment.