Latest news and publications from inflammation and infections group.
Hiking trip in the Nuuksio National Park 13th of October together with Seppo Meri's group
17th European Meeting on Complement in Human Disease (EMCHD 2019) participants (Spain,14-17 September, 2019): Larisa Viazmina, Karita Haapasalo and Shahan Syed
Syed, S et al. Role of Pneumococcal NanA Neuraminidase Activity in Peripheral Blood
Schematic illustration of the putative mechanism how NanA could reduce complement regulation by factor H on the cells and sensitize cells for attack by complement and thereby lead to cell damage. In addition, NanA increases the susceptibility of cells to attack by pneumolysin (PLY) or other virulence factors.
Haapasalo, K. et al. Staphylococcus aureus toxin LukSF dissociates from its membrane receptor target to enable renewed ligand sequestration. October 2018. The FASEB Journal
Model for LukSF-receptor binding and the mechanism of LukSF-induced inflammation. (A). LukS (PDB ID: 1T5R) binds on hC5aR (structure based on angiotensin receptor data PDB ID: 4YAY, cyan dashed box) as a soluble monomer on the cell membrane. Each LukS monomer binds one hC5aR molecule via the receptor interacting residues R73, Y184, Y250, T244 (marked with blue dots) within a cluster of approximately 4-5 hC5aR homo-oligomers. Upon binding to hC5aR LukS exposes residues for LukF (PDB ID: 1LKF) binding (interface indiacted by dashed ellipse). In these tight clusters each LukF can bind to two LukS monomers via two interfaces. (B) Binding of LukF on LukS and formation of the octameric pore (PDB ID: 3B07) causes dissociation of the receptors from the complex because of leakage of the cell membrane and possibly also since the receptor binding region (marked with a circle) is buried between the monomers in the complex. (C) The detached hC5aR molecule can be reused by its ligands LukS or C5a anaphylatoxin (PDB ID: 1KJS). (D) Zoom out of (A-C), illustrating the putative mechanism of LukSF induced inflammation.
Eija Nissilä, E et al. Complement factor H and apolipoprotein E participate in regulation of inflammation in THP-1 macrophages, Front. Immunol. 2018. doi: 10.3389/fimmu.2018.02701
Schematic illustrating the putative mechanism of the effect of factor H-apoE interaction in reducing inflammation in atherosclerotic lesions. Binding of factor H on apoE containing HDL particles reduces plasma complement activation while elevated binding of apoE on monocytes/macrophages/foam cells via FH reduces local inflammation and cholesterol efflux.