Resident macrophages acquire innate immune memory in staphylococcal skin infection.

Abstract

<i>Staphylococcus aureus (S. aureus)</i> is a common colonizer of healthy skin and mucous membranes. At the same time, <i>S. aureus</i> is the most frequent cause of skin and soft tissue infections. Dermal macrophages (Mφ) are critical for the coordinated defense against invading <i>S. aureus,</i> yet they have a limited life span with replacement by bone marrow derived monocytes. It is currently poorly understood whether localized <i>S. aureus</i> skin infections persistently alter the resident Mφ subset composition and resistance to a subsequent infection. In a strictly dermal infection model we found that mice, which were previously infected with <i>S. aureus</i>, showed faster monocyte recruitment, increased bacterial killing and improved healing upon a secondary infection. However, skin infection decreased Mφ half-life, thereby limiting the duration of memory. In summary, resident dermal Mφ are programmed locally, independently of bone marrow-derived monocytes during staphylococcal skin infection leading to transiently increased resistance against a second infection.