A skin isolate of Micrococcus luteus negates the Staphylococcus aureus-induced release of type 2 cytokines from keratinocytes

TL;DR

A skin bacterium, Micrococcus luteus, prevents a harmful immune response caused by Staphylococcus aureus, which is linked to eczema in atopic dermatitis.

Contribution

Identifies a specific serine protease from Micrococcus luteus that inhibits S. aureus-induced cytokine release in keratinocytes.

Findings

Micrococcus luteus uniquely prevents IL-33 and TSLP release from keratinocytes triggered by S. aureus.

The active factor is a serine protease called PADP, which degrades S. aureus's Sbi and IL-33.

The M. luteus type strain lacks functional PADP due to a frameshift mutation in its active site.

Abstract

Staphylococcus aureus second immunoglobulin-binding protein (Sbi) is a unique type 2-promoting virulence factor that induces IL-33 and thymic stromal lymphopoietin (TSLP) release. This mechanism is essential for the development of S. aureus–induced eczema in the widely used NC/Tnd mouse model of human atopic dermatitis (AD). Microbiome shifts in AD suggest that microbiota could modulate the disease. We therefore sought to identify skin bacteria that attenuate S. aureus-induced IL-33/TSLP release from keratinocytes. Micrococcus luteus was unique among skin isolates in its ability to negate cytokine induction. The bioactive factor responsible was identified using fractionation, LC-MS and recombinant proteins, as the serine protease “PA domain protein” (PADP). Immunoblotting and ELISA confirmed Sbi and IL-33 degradation by PADP. This was not observed with the M. luteus type strain which contains a frame shift mutation within the PADP active site. These data provide new insights into the role of skin microbiota in AD and highlights their potential as topical therapeutics.

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