An ecoimmunological approach to study evolutionary and ancient links between coagulation, complement and Innate immunity

Virulence
Praveen PapareddyHeiko Herwald

Abstract

Coagulation, complement, and innate immunity are tightly interwoven and form an alliance that can be traced back to early eukaryotic evolution. Here we employed an ecoimmunological approach using Tissue Factor Pathway Inhibitor (TFPI)-1-derived peptides from the different classes of vertebrates (i.e. fish, reptile, bird, and mammals) and tested whether they can boost killing of various human bacterial pathogens in plasma. We found signs of species-specific conservation and diversification during evolution in these peptides that significantly impact their antibacterial activity. Though all peptides tested executed bactericidal activity in mammalian plasma (with the exception of rodents), no killing was observed in plasma from birds, reptiles, and fish, pointing to a crucial role for the classical pathway of the complement system. We also observed an interference of these peptides with the human intrinsic pathway of coagulation though, unlike complement activation, this mechanism appears not to be evolutionary conserved.

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Citations

Sep 27, 2018·Frontiers in Immunology·Mohamad N AliPraveen Papareddy
Apr 21, 2021·Proceedings of the National Academy of Sciences of the United States of America·Matthew L HoldingChristopher L Parkinson
May 9, 2021·Medical Hypotheses·Sarai M KeestraGul Deniz Salali
Jun 8, 2021·Frontiers in Cellular and Infection Microbiology·Hilger JagauHeiko Herwald

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Methods Mentioned

BETA
Surface plasmon resonance
chip
Assay

Software Mentioned

BIA evaluation
ClusPro
JPred4
PEPFOLD
AMBER
Blosum
GraphPad Prism
Mega6
PSIPRED
ClustalW

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