speb of streptococcus pyogenes differentially modulates antibacterial and receptor activating properties of human chemokinesspeb酿脓链球菌的不同调节抗菌和人类趋化因子受体激活的属性.pdfVIP

SpeB of Streptococcus pyogenes Differentially Modulates Antibacterial and Receptor Activating Properties of Human Chemokines 1 2 1¤a 2¤b ¨ 2 Arne Egesten , Anders I. Olin , Helena M. Linge , Manisha Yadav , Matthias Morgelin , Anna 3 2 Karlsson , Mattias Collin * 1 Division of Respiratory Medicine, Department of Clinical Sciences Lund, Lund University, Lund, Sweden, 2 Division of Infection Medicine, Department of Clinical Sciences ¨ ¨ Lund, Lund University, Lund, Sweden, 3 Department of Rheumatology and Inflammation Research, University of Goteborg, Goteborg, Sweden Abstract Background: CXC chemokines are induced by inflammatory stimuli in epithelial cells and some, like MIG/CXCL9, IP–10/ CXCL10 and I–TAC/CXCL11, are antibacterial for Streptococcus pyogenes. Methodology/Principal Findings: SpeB from S. pyogenes degrades a wide range of chemokines (i.e. IP10/CXCL10, I-TAC/ CXCL11, PF4/CXCL4, GROa/CXCL1, GRO b/CXCL2, GROc/CXCL3, ENA78/CXCL5, GCP-2/CXCL6, NAP-2/CXCL7, SDF-1/CXCL12, BCA-1/CXCL13, BRAK/CXCL14, SRPSOX/CXCL16, MIP-3a/CCL20, Lymphotactin/XCL1, and Fractalkine/CX3CL1), has no activity on IL-8/CXCL8 and RANTES/CCL5, partly degrades SRPSOX/CXCL16 and MIP-3a/CCL20, and releases a 6 kDa CXCL9 fragment. CXCL10 and CXCL11 loose receptor activating and antibacterial activities, while the CXCL9 fragment does not activate the receptor CXCR3 but retains its antibacterial activity. Conclusions/Significance: SpeB destroys most of the signaling and antibacterial properties of chemoki