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Transient Binding Dynamics of Complement System Pattern Recognition Molecules on Pathogens.

Maximilian Peter GötzMario Alejandro Duque VillegasBeatrice FagerängAileen KerfinMikkel-Ole SkjoedtPeter GarredAnne Rosbjerg
Published in: Journal of immunology (Baltimore, Md. : 1950) (2024)
Previous studies of pattern recognition molecules (PRMs) of the complement system have revealed difficulties in observing binding on pathogens such as Aspergillus fumigatus and Escherichia coli, despite complement deposition indicative of classical and lectin pathway activation. Thus, we investigated the binding dynamics of PRMs of the complement system, specifically C1q of the classical pathway and mannose-binding lectin (MBL) of the lectin pathway. We observed consistently increasing deposition of essential complement components such as C4b, C3b, and the terminal complement complex on A. fumigatus and E. coli. However, C1q and MBL binding to the surface rapidly declined during incubation after just 2-4 min in 10% plasma. The detachment of C1q and MBL can be linked to complement cascade activation, as the PRMs remain bound in the absence of plasma. The dissociation and the fate of C1q and MBL seem to have different mechanistic functions. Notably, C1q dynamics were associated with local C1 complex activation. When C1s was inhibited in plasma, C1q binding not only remained high but further increased over time. In contrast, MBL binding was inversely correlated with total and early complement activation due to MBL binding being partially retained by complement inhibition. Results indicate that detached MBL might be able to functionally rebind to A. fumigatus. In conclusion, these results reveal a (to our knowledge) novel "hit-and-run" complement-dependent PRM dynamic mechanism on pathogens. These dynamics may have profound implications for host defense and may help increase the functionality and longevity of complement-dependent PRMs in circulation.
Keyphrases
  • escherichia coli
  • healthcare
  • binding protein
  • computed tomography
  • gene expression
  • gram negative
  • pseudomonas aeruginosa
  • high resolution
  • transcription factor
  • dna methylation
  • contrast enhanced