TY - JOUR
T1 - Staphylococcus aureus proteases trigger eosinophil-mediated skin inflammation
AU - Kline, Sabrina N.
AU - Orlando, Nicholas A.
AU - Lee, Alex J.
AU - Wu, Meng Jen
AU - Zhang, Jing
AU - Youn, Christine
AU - Feller, Laine E.
AU - Pontaza, Cristina
AU - Dikeman, Dustin
AU - Limjunyawong, Nathachit
AU - Williams, Kaitlin L.
AU - Wang, Yu
AU - Cihakova, Daniela
AU - Jacobsen, Elizabeth A.
AU - Durum, Scott K.
AU - Garza, Luis A.
AU - Dong, Xinzhong
AU - Archer, Nathan K.
PY - 2024/2/6
Y1 - 2024/2/6
N2 - Staphylococcus aureus skin colonization and eosinophil infiltration are associated with many inflammatory skin disorders, including atopic dermatitis, bullous pemphigoid, Netherton's syndrome, and prurigo nodularis. However, whether there is a relationship between S. aureus and eosinophils and how this interaction influences skin inflammation is largely undefined. We show in a preclinical mouse model that S. aureus epicutaneous exposure induced eosinophil-recruiting chemokines and eosinophil infiltration into the skin. Remarkably, we found that eosinophils had a comparable contribution to the skin inflammation as T cells, in a manner dependent on eosinophil-derived IL-17A and IL-17F production. Importantly, IL-36R signaling induced CCL7-mediated eosinophil recruitment to the inflamed skin. Last, S. aureus proteases induced IL-36α expression in keratinocytes, which promoted infiltration of IL-17-producing eosinophils. Collectively, we uncovered a mechanism for S. aureus proteases to trigger eosinophil-mediated skin inflammation, which has implications in the pathogenesis of inflammatory skin diseases.
AB - Staphylococcus aureus skin colonization and eosinophil infiltration are associated with many inflammatory skin disorders, including atopic dermatitis, bullous pemphigoid, Netherton's syndrome, and prurigo nodularis. However, whether there is a relationship between S. aureus and eosinophils and how this interaction influences skin inflammation is largely undefined. We show in a preclinical mouse model that S. aureus epicutaneous exposure induced eosinophil-recruiting chemokines and eosinophil infiltration into the skin. Remarkably, we found that eosinophils had a comparable contribution to the skin inflammation as T cells, in a manner dependent on eosinophil-derived IL-17A and IL-17F production. Importantly, IL-36R signaling induced CCL7-mediated eosinophil recruitment to the inflamed skin. Last, S. aureus proteases induced IL-36α expression in keratinocytes, which promoted infiltration of IL-17-producing eosinophils. Collectively, we uncovered a mechanism for S. aureus proteases to trigger eosinophil-mediated skin inflammation, which has implications in the pathogenesis of inflammatory skin diseases.
KW - eosinophils
KW - inflammatory skin diseases
KW - interleukin-17
KW - interleukin-36
KW - Staphylococcus aureus
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UR - http://www.scopus.com/inward/citedby.url?scp=85183692375&partnerID=8YFLogxK
U2 - 10.1073/pnas.2309243121
DO - 10.1073/pnas.2309243121
M3 - Article
C2 - 38289950
AN - SCOPUS:85183692375
SN - 0027-8424
VL - 121
SP - e2309243121
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 6
ER -