Interaction of the Human Contact System with Pathogens—An Update

Abstract

The name human contact system is related to its mode of action, as “contact” with artificial negatively charged surfaces triggers its activation. Today, it is generally believed that the contact system is an inflammatory response mechanism not only against artificial material but also against misfolded proteins and foreign organisms. Upon activation, the contact system is involved in at least two distinct (patho)physiologic processes:i. the trigger of the intrinsic coagulation via factor XI and ii. the cleavage of high molecular weight kininogen with release of bradykinin and antimicrobial peptides (AMPs). Bradykinin is involved in the regulation of inflammatory processes, vascular permeability, and blood pressure. Due to the release of AMPs, the contact system is regarded as a branch of the innate immune defense against microorganisms. There is an increasing list of pathogens that interact with contact factors, in addition to bacteria also fungi and viruses bind and activate the system. In spite of that, pathogens have developed their own mechanisms to activate the contact system, resulting in manipulation of this host immune response. In this up-to-date review, we summarize present research on the interaction of pathogens with the human contact system, focusing particularly on bacterial and viral mechanisms that trigger inflammation via contact system activation.

Airways exudation of plasma macromolecules: Innate defense, epithelial regeneration, and asthma

“…86 It has been suggested that both viral and bacterial pathogens increase microvascular permeability in part through activation of the ''contact system,'' causing release of the vasoactive autacoid bradykinin. 87 Mechanisms involving endothelial Toll-like receptors 2, 4, and 9 have also been reported to be involved in the increased vascular permeability caused by bacterial infection, but these mechanisms concern pathophysiology of sepsis with no known relevance to mucosal defense. 88 Innovative in vivo approaches seem required to explore the possibility that disease-inducing microbes deposited on the intact mucosal surface can evoke highly localized plasma exudation responses.…”

Peptidylarginine Deiminase of Porphyromonas gingivalis Modulates the Interactions between Candida albicans Biofilm and Human Plasminogen and High-Molecular-Mass Kininogen

“…This includes the modulation of important host plasma homeostatic systems such as the coagulation and fibrinolysis systems, the complement system, and the kinin generation system (also known as the contact system) [45,46,[49][50][51][52]. One of the mechanisms that facilitates the interference by pathogens of plasma homeostatic systems is the binding of their individual components to the surfaces of microbial cells, which contributes to the local increase in their concentration and further processing by proteases, or to the insidious takeover of these components and their exclusion from the host systems [53,54]. Such abilities to entrain plasma cascades and thus evade host innate immunity were previously described for the opportunistic pathogen C. albicans [55,56].…”

Prothrombotic and Proinflammatory Activities of the β-Hemolytic Group B Streptococcal Pigment

“…Incubation of bacteria with human plasma did not induce clotting after recalcification, suggesting that induction of blood clotting by GBS is mainly dependent on human cellular components. As certain pathogenic bacteria are able to activate the human contact system [10], bacteria were incubated with human plasma, and activation of contact system proteases at the bacterial surface was assessed. Only LUMC16 showed FXIIa/PK activity at the bacterial surface (Fig.…”

“…The human contact system consists of two main proteases, factor XII (FXII) and plasma prekallikrein, and one nonenzymatic cofactor, highmolecular-weight kininogen. Any foreign biological or artificial surfaces activate FXII, which in turn activates coagulation factor XI (FXI), resulting in subsequent thrombus formation [10]. There is a close relationship to DIC and systemic inflammatory responses.…”