Hyaluronan Degradation by Cemip Regulates Host Defense against Staphylococcus aureus Skin Infection

• Main Authors: Tatsuya Dokoshi, Ling-juan Zhang, Fengwu Li, Teruaki Nakatsuji, Anna Butcher, Hiroyuki Yoshida, Masayuki Shimoda, Yasunori Okada, Richard L. Gallo
• Format: Article
• Language: English
• Published: Elsevier 2020-01-01
• Series: Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124719316407

Summary: Staphylococcus aureus is a major human bacterial pathogen responsible for deep tissue skin infections. Recent observations have suggested that rapid, localized digestion of hyaluronic acid in the extracellular matrix (ECM) of the dermis may influence bacterial invasion and tissue inflammation. In this study we find that cell migration-inducing protein (Cemip) is the major inducible gene responsible for hyaluronan catabolism in mice. Cemip−/− mice failed to digest hyaluronan and had significantly less evidence of infection after intradermal bacterial challenge by S. aureus. Stabilization of large-molecular-weight hyaluronan enabled increased expression of cathelicidin antimicrobial peptide (Camp) that was due in part to enhanced differentiation of preadipocytes to adipocytes, as seen histologically and by increased expression of Pref1, PPARg, and Adipoq. Cemip−/− mice challenged with S. aureus also had greater IL-6 expression and neutrophil infiltration. These observations describe a mechanism for hyaluronan in the dermal ECM to regulate tissue inflammation and host antimicrobial defense. : In this paper, Dokoshi et al. describe how the mammalian hyaluronidase Cemip is induced in the dermis during S. aureus infection. Cemip digests hyaluronan in the skin to regulate reactive adipogenesis and subsequent antimicrobial activity and skin inflammation. Keywords: skin, Staphylococcus aureus, dermis, cathelicidin, antimicrobial peptides, innate immunity, hyaluronan, glycosaminoglycans