Sterile inflammation in crystallopathies

Project management: Dr. Konstantin Neumann

Phone: 0511 532 5284
Mobile: (MHH-internal): 17-2246
(from outside): 0176 1532 2246
email: neumann.konstantin@mh-hannover.de

 

Research concept:

Inflammation in gout is almost indistinguishable in its nature and severity from inflammation caused by bacteria or yeasts. While the proteins that recognize bacteria and yeasts are largely known, it is still unclear how the immune system recognizes gout crystals and other sterile structures.

As a PostDoc, I found an immune receptor (Clec12A) that specifically recognizes gout crystals but slows down inflammation. Now, with C-reactive protein (CRP) innate immunoglobulins of the IgM type, we have identified two immune recognition molecules that recognize uric acid crystals and activate the complement system and thus the innate immune system.

Thus, the immune system appears to interact with microbes and crystals in a similar way.


Uric acid crystals
Uric acid crystals from: Alberts et al. Scientific Reports. 2020;10:6391.

CRP recognizes uric acid crystals and recruits the innate immune system: Microscopy of a uric acid crystal on which the bound protein CRP (red) and complement C3 (green) are stained. The colocalization of CRP and C3 is visible through the yellow staining. Complement C3 is a central protein of the innate immune system. Adapted from Alberts et al. 2020 Scientific Reports.

 

 

Funding: DGKL

 

Selected publications:

  • Saller BS, Wöhrle S, Fischer L, Dufossez C, Ingerl IL, Kessler S, Mateo-Tortola M, Gorka O, Lange F, Cheng Y, Neuwirt E, Marada A, Koentges C, Urban C, Aktories P, Reuther P, Giese S, Kirschnek S, Mayer C, Pilic J, Falquez-Medina H, Oelgeklaus A, Deepagan VG, Shojaee F, Zimmermann JA, Weber D, Tai YH, Crois A, Ciminski K, Peyronnet R, Brandenburg KS, Wu G, Baumeister R, Heimbucher T, Rizzi M, Riedel D, Helmstädter M, Buescher J, Neumann K, Misgeld T, Kerschensteiner M, Walentek P, Kreutz C, Maurer U, Rambold AS, Vince JE, Edlich F, Malli R, Häcker G, Kierdorf K, Meisinger C, Köttgen A, Jakobs S, Weber ANR, Schwemmle M, Groß CJ, Groß O. Acute suppression of mitochondrial ATP production prevents apoptosis and provides an essential signal for NLRP3 inflammasome activation. Immunity. 2025 Jan 14;58(1):90-107.e11
  • Wessig AK, Hoffmeister L, Klingberg A, Alberts A, Pich A, Brand K, Witte T, Neumann K. Natural antibodies and CRP drive anaphylatoxin production by urate crystals.
    Sci Rep. 2022 Mar 16;12(1):4483.
  • Alberts A, Klingberg A, Hoffmeister L, Wessig AK, Brand K, Pich A, Neumann K. Binding of Macrophage Receptor MARCO, LDL, and LDLR to Disease-Associated Crystalline Structures.
    Front Immunol. 2020 Dec 8;11:596103.
  • Alberts A, Klingberg A, Wessig AK, Combes C, Witte T, Brand K, Pich A, Neumann K. C-reactive protein (CRP) recognizes uric acid crystals and recruits proteases C1 and MASP1.
    Sci Rep. 2020 Apr14;10(1):6391.
  • Neumann K, Castiñeiras-Vilariño M, Höckendorf U, Hannesschläger N, Lemeer S, Kupka D, Meyermann S, Lech M, Anders HJ, Kuster B, Busch DH, Gewies A, Naumann R, Groß O, Ruland J. Clec12a is an inhibitory receptor for uric acid crystals that regulates inflammation in response to cell death. Immunity. 2014 Mar 20;40(3):389-99.
  • Strasser D*, Neumann K*, Bergmann H, Marakalala MJ, Guler R, Rojowska A, Hopfner KP, Brombacher F, Urlaub H, Baier G, Brown GD, Leitges M, Ruland J. Syk kinase-coupled C-type lectin receptors engage protein kinase C-δ to elicit Card9 adaptor-mediated innate immunity. Immunity. 2012 Jan 27;36(1):32-42
    *These authors contributed equally to this work.