TY  - JOUR
A1  - Dasari, Prasad
A1  - Koleci, Naile
A1  - Shopova, Iordana A.
A1  - Wartenberg, Dirk
A1  - Beyersdorf, Niklas
A1  - Dietrich, Stefanie
A1  - Sahagún-Ruiz, Alfredo
A1  - Figge, Marc Thilo
A1  - Skerka, Christine
A1  - Brakhage, Axel A.
A1  - Zipfel, Peter F.
T1  - Enolase from Aspergillus fumigatus is a moonlighting protein that binds the human plasma complement proteins factor H, FHL-1, C4BP, and plasminogen
JF  - Frontiers in Immunology
N2  - The opportunistic fungal pathogen Aspergillus fumigatus can cause severe infections, particularly in immunocompromised individuals. Upon infection, A. fumigatus faces the powerful and directly acting immune defense of the human host. The mechanisms on how A. fumigatus evades innate immune attack and complement are still poorly understood. Here, we identify A. fumigatus enolase, AfEno1, which was also characterized as fungal allergen, as a surface ligand for human plasma complement regulators. AfEno1 binds factor H, factor-H-like protein 1 (FHL-1), C4b binding protein (C4BP), and plasminogen. Factor H attaches to AfEno1 via two regions, via short conserved repeats (SCRs) 6–7 and 19–20, and FHL-1 contacts AfEno1 via SCRs 6–7. Both regulators when bound to AfEno1 retain cofactor activity and assist in C3b inactivation. Similarly, the classical pathway regulator C4BP binds to AfEno1 and bound to AfEno1; C4BP assists in C4b inactivation. Plasminogen which binds to AfEno1 via lysine residues is accessible for the tissue-type plasminogen activator (tPA), and active plasmin cleaves the chromogenic substrate S2251, degrades fibrinogen, and inactivates C3 and C3b. Plasmin attached to swollen A. fumigatus conidia damages human A549 lung epithelial cells, reduces the cellular metabolic activity, and induces cell retraction, which results in exposure of the extracellular matrix. Thus, A. fumigatus AfEno1 is a moonlighting protein and virulence factor which recruits several human regulators. The attached human regulators allow the fungal pathogen to control complement at the level of C3 and to damage endothelial cell layers and tissue components.
KW  - complement factor H
KW  - moonlighting
KW  - immune evasion
KW  - plasminogen
KW  - blocking phagocytosis
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195612
SN  - 1664-3224
VL  - 10
ER  -