Systemic complement researchVerschoor Lab Member
Welcome to the Verschoor-laboratory for systemic complement research!
Our group explores how the complement system directs the developing immune response, by facilitating physical contact between cells of the immune system and pathogens or other immunogenic targets.
The complement system labels potential immune-targets in a process known as opsonization. The majority of opsonizing “tags” is complement factor C3-derived, giving cells bearing C3-specific complement receptors (CR) a key role in the developing immune response. CRs are expressed on a wide variety of (immune) cells in diverse organ systems, ranging from CR1 on circulating erythrocytes to CRIg on hepatic Kupffer Cells, and from CR2 on splenic B cells to CR4 on dermal Dendritic Cells. Depending on the cell population, complement opsonized targets can be captured, transported, phagocytosed, destroyed, or processed to be presented to other immune cells. Thus, this complement-directed network of cells and processes impacts the development of protective immunity and, in some settings, contributes to autoimmunity or the immunopathology of systemic infections.
To gain insight into the physical and dynamic processes that underlie the immunoregulatory impact of complement, our laboratory develops and applies sophisticated imaging techniques. We visualize and quantify complement-driven processes, including capture, transport, and distribution of pathogens and antigens, correlating such parameters to the immunological outcome.
Using this approach, we identified complement as critical factor allowing multinucleated giant cells to phagocytose and eliminate pathogenic protein deposits that characterize amyloidosis or Alzheimer’s disease (see 1, or listen to our Cell Press podcast interview starting at 9.35min). We also showed that complement-driven platelet adherence to intravascular bacteria establishes a “dual-track clearance” process that balances innate and adaptive antibacterial immune mechanisms (see 2, recognized by the German Sepsis Society with the Schottmüller Award 2017). Our lab also identified platelet GPIb as immune adherence receptor, impacting cytotoxic antibacterial immunity (see 3, and a "news and views" highlight in Nature Immunology), prompting us to continue exploring connections between immunity and hemostasis, for their mutual impact on protective and deleterious mechanisms in bacteremia and sepsis (see 4-6).
With the advent of complement-therapeutics in the clinic, our fundamental insights into complement-driven immune processes also offer perspectives toward new strategies to strengthen protective immunity, control autoimmunity and reduce immunopathology.
(1) Multinucleated Giant Cells Are Specialized for Complement-Mediated Phagocytosis and Large Target Destruction. Milde R, Ritter J, Tennent GA, Loesch A, Martinez FO, Gordon S, Pepys MB, Verschoor A, Helming L. Cell Rep.2015 Dec 1;13(9):1937-48.
(2) Dual-Track Clearance of Circulating Bacteria Balances Rapid Restoration of Blood Sterility with Induction of Adaptive Immunity. Broadley SP, Plaumann A, Coletti R, Lehmann C, Wanisch A, Seidlmeier A, Esser K, Luo S, Rämer PC, Massberg S, Busch DH, van Lookeren Campagne M, Verschoor A. Cell Host Microbe. 2016 Jul 13;20(1):36-48.
(3) A platelet-mediated system for shuttling blood-borne bacteria to CD8α+ dendritic cells depends on glycoprotein GPIb and complement C3. Verschoor A, Neuenhahn M, Navarini AA, Graef P, Plaumann A, Seidlmeier A, Nieswandt B, Massberg S, Zinkernagel RM, Hengartner H, Busch DH. Nat Immunol. 2011 Oct 30;12(12):1194-201.
(4) Pathogen clearance and immune adherence "revisited": Immuno-regulatory roles for CRIg. van Lookeren Campagne M, Verschoor A. Semin Immunol. 2018 Jun;37:4-11.
(5) Complement and coagulation: so close, yet so far. Schmidt CQ, Verschoor A. Blood. 2017 Dec 14;130(24):2581-2582.
(6) Crosstalk between platelets and the complement system in immune protection and disease. Verschoor A, Langer HF. Thromb Haemost. 2013 Nov;110(5):910-9.