Staphylococcus aureus-derived staphopain B, a potent cysteine protease activator of plasma chemerin.
Chemerin is an attractant for cells that express the serpentine receptor CMKLR1, which include immature plasmacytoid dendritic cells (pDC) and macrophages. Chemerin circulates in the blood where it exhibits low biological activity, but upon proteolytic cleavage of its C terminus, it is converted to a potent chemoattractant. Enzymes that contribute to this conversion include host serine proteases of the coagulation, fibrinolytic, and inflammatory cascades, and it has been postulated that recruitment of pDC and macrophages by chemerin may serve to balance local tissue immune and inflammatory responses. In this work, we describe a potent, pathogen-derived proteolytic activity capable of chemerin activation. This activity is mediated by staphopain B (SspB), a cysteine protease secreted by Staphylococcus aureus. Chemerin activation is triggered by growth medium of clinical isolates of SspB-positive S. aureus, but not by that of a SspB(null) mutant. C-terminal processing by SspB generates a chemerin isoform identical with the active endogenous attractant isolated from human ascites fluid. Interestingly, SspB is a potent trigger of chemerin even in the presence of plasma inhibitors. SspB may help direct the recruitment of specialized host cells, including immunoregulatory pDC and/or macrophages, contributing to the ability of S. aureus to elicit and maintain a chronic inflammatory state.
Kulig
Paulina
P
Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Ulica.Gronostajowa 7, 30-387 Krakow, Poland.
Zabel
Brian A
BA
Dubin
Grzegorz
G
Allen
Samantha J
SJ
Ohyama
Takao
T
Potempa
Jan
J
Handel
Tracy M
TM
Butcher
Eugene C
EC
Cichy
Joanna
J
D000818:Animals; D001201:Ascites / Q000276:immunology; D018925:Chemokines / Q000276:immunology*; D002633:Chemotaxis / Q000276:immunology; D002908:Chronic Disease; D003546:Cysteine Endopeptidases / Q000172:deficiency / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D020536:Enzyme Activators / Q000276:immunology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008264:Macrophages / Q000276:immunology; D051379:Mice; D010949:Plasma / Q000276:immunology; D019707:Receptors, Chemokine / Q000276:immunology; D043562:Receptors, G-Protein-Coupled / Q000276:immunology; D013203:Staphylococcal Infections / Q000276:immunology*; D013211:Staphylococcus aureus / Q000235:genetics / Q000276:immunology*
C102741:CMKLR1 protein, human; C486456:CMKLR1 protein, mouse; D018925:Chemokines; D020536:Enzyme Activators; D036341:Intercellular Signaling Peptides and Proteins; C478630:RARRES2 protein, human; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; D003546:Cysteine Endopeptidases; C479137:staphopain B protein, Staphylococcus aureus