Interplays between inflammasomes and viruses, bacteria (pathogenic and probiotic), yeasts and parasites

Abstract

In recent years, scientists studying the molecular mechanisms of inflammation have discovered an amazing phenomenon - the inflammasome - a component of the innate immune system that can regulate the functional activity of effector cells during inflammation. At present, it is known that inflammasomes are multimolecular complexes (cytosolic multiprotein oligomers of the innate immune system) that contain many copies of receptors recognizing the molecular structures of cell-damaging factors and pathogenic agents. Inflammasomes are mainly formed in myeloid cells, and their main function is participation in the cleavage of the pro-IL-1β and pro-IL-18 cytokines into their biologically active forms (IL-1β, IL-18). Each type of microorganism influences particular inflammasome activation, and long-term exposure of the organism to viruses, bacteria, yeasts or parasites, among others, can induce uncontrolled inflammation and autoinflammatory diseases. Therefore, this review aims to present the most current scientific data on the molecular interplay between inflammasomes and particular microorganisms. Knowledge about the mechanisms responsible for the interaction between the host and certain types of microorganisms could contribute to the individuation of innovative strategies for the treatment of uncontrolled inflammation targeting a specific type of inflammasome activated by a specific type of pathogen.

Keywords: Coronaviruses; Inflammasomes; Parasites; Pathogenic and probiotic bacteria; Viruses; Yeasts.

Fig. 1

NLRP3 inflammasome composition. The NLRP3 inflammasome contains the following domains: LRR (leucine-rich repeat domain), NAD (binding domain), NACHT(nucleotide-binding and oligomerization domain); PYD (pyrin domain), CARD (caspase recruitment domain). Pathogenic components and endogenous cytokines trigger NLRP3 inflammasome activation. Active NLRP3 inflammasome initiate activation caspase-1, which causes the transformation of pro-IL-1β and pro-IL-18 cytokines into IL-1 β and IL-18. Caspase-1 can also cleave gasdermin D protein, initiating cell death termed as pyroptosis.

Fig. 2

The scheme of NLRP3 inflammasome activation. For NLRP3 inflammasome formation, two signals are needed. The sources of the first signal are microbial components and endogenous cytokines (PAMPs or DAMPs). Here, the ligands of the Toll-like receptor (e.g., LPS) activates NFκB, leading to the expression of NLRP3 protein and upregulation of pro-IL-1β and pro-IL-18 synthesis. The second signal is transmitted, for example, by extracellular ATP molecules (1), reactive oxygen species (ROS) generation (2) or environmental irritants form intracellular crystalline (3). These agents activate the NLRP3 expression to first cause NLRP3 protein oligomerization and then ASC oligomerization, leading to the formation of the NLRP3 inflammasome. Inside the formed NLRP3 inflammasome, autoproteolysis of pro-caspase-1 leads to the creation of an active caspase-1, which in turn cleaves pro-IL-1β and pro-IL-18 into active IL-1β and IL-18.

Fig. 3

AIM2 inflammasome composition. The AIM2 inflammasome contains the following domains: HIN-200 domain; PYD (pyrin domain), CARD (caspase recruitment domain). During AIM2 inflammasome activation, the AIM2 protein functions as an initiating component that recognizes the cytoplasmically located dsDNA (DNA-binding HIN-200 domain), whereas the ASC protein functions as the pro-caspase-1 activator and caspase-1 as an effector component. Active AIM2 inflammasome initiate activation caspase-1, which causes the transformation of pro-IL-1β and pro-IL-18 cytokines into IL-1 β and IL-18 and induction of pyroptosis.