Staphylococcus epidermidis-Derived Protease Esp Mediates Proteolytic Activation of Pro‒IL-1β in Human Keratinocytes
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Staphylococcus epidermidis-Derived Protease Esp Mediates Proteolytic Activation of Pro‒IL-1β in Human Keratinocytes. / Rademacher, Franziska; Bartels, Joachim; Gläser, Regine; Rodewald, Meno; Schubert, Sabine; Drücke, Daniel; Rohde, Holger; Harder, Jürgen.
In: J INVEST DERMATOL, Vol. 142, No. 10, 10.2022, p. 2756-2765.e8.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Staphylococcus epidermidis-Derived Protease Esp Mediates Proteolytic Activation of Pro‒IL-1β in Human Keratinocytes
AU - Rademacher, Franziska
AU - Bartels, Joachim
AU - Gläser, Regine
AU - Rodewald, Meno
AU - Schubert, Sabine
AU - Drücke, Daniel
AU - Rohde, Holger
AU - Harder, Jürgen
N1 - Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2022/10
Y1 - 2022/10
N2 - The Gram-positive bacterium Staphylococcus epidermidis (SE) is an abundant skin commensal. It plays an important role in cutaneous defense by activation of IL-1 signaling. In keratinocytes (KCs), SE induces the release of mature IL-1β. IL-1β serves as an important cytokine of host defense. It contains an N-terminal prodomain that has to be cleaved off to generate active mature IL-1β. Typically, the processing and release of IL-1β are associated with inflammasome assembly and activation of the protease caspase-1. In this study, we report that the bacterial challenge of KCs with SE induced the release of mature IL-1β in a caspase-1‒independent manner. Instead, the SE-derived serine protease Esp was identified as a pro‒IL-1β‒processing factor leading to a proteolytic maturation of active IL-1β. Esp production and secretion by various SE strains correlated with their capacity to induce the release of mature IL-1β in human primary KCs. Reconstitution of Esp-lacking SE strains with Esp enhanced their capacity to induce IL-1β release in KCs and skin. Intracellular abundance of pro‒IL-1β and cytotoxic effects of SE suggest a release of pro‒IL-1β during injury, followed by extracellular Esp-mediated processing to mature IL-1β. These findings provide further insights into how a skin commensal interacts with KCs to activate cutaneous host innate defense.
AB - The Gram-positive bacterium Staphylococcus epidermidis (SE) is an abundant skin commensal. It plays an important role in cutaneous defense by activation of IL-1 signaling. In keratinocytes (KCs), SE induces the release of mature IL-1β. IL-1β serves as an important cytokine of host defense. It contains an N-terminal prodomain that has to be cleaved off to generate active mature IL-1β. Typically, the processing and release of IL-1β are associated with inflammasome assembly and activation of the protease caspase-1. In this study, we report that the bacterial challenge of KCs with SE induced the release of mature IL-1β in a caspase-1‒independent manner. Instead, the SE-derived serine protease Esp was identified as a pro‒IL-1β‒processing factor leading to a proteolytic maturation of active IL-1β. Esp production and secretion by various SE strains correlated with their capacity to induce the release of mature IL-1β in human primary KCs. Reconstitution of Esp-lacking SE strains with Esp enhanced their capacity to induce IL-1β release in KCs and skin. Intracellular abundance of pro‒IL-1β and cytotoxic effects of SE suggest a release of pro‒IL-1β during injury, followed by extracellular Esp-mediated processing to mature IL-1β. These findings provide further insights into how a skin commensal interacts with KCs to activate cutaneous host innate defense.
U2 - 10.1016/j.jid.2022.04.010
DO - 10.1016/j.jid.2022.04.010
M3 - SCORING: Journal article
C2 - 35490742
VL - 142
SP - 2756-2765.e8
JO - J INVEST DERMATOL
JF - J INVEST DERMATOL
SN - 0022-202X
IS - 10
ER -
