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. 2023 Jul 11;17:1216489. doi: 10.3389/fnins.2023.1216489

Figure 2.

Figure 2

(A) Complement activation with the formation of the C5b-9(n) leading to the formation of a MAC/PFTs complex. The fully formed MAC creates large, 10 nm-wide pores initiating an ion flux cumulating in a calcium dependent cell lysis. As a result of cell lysis, high concentrations of ATP may be released into the local environment which can simulate P2X and activate downstream purinergic modification. Extracellular ATP similarly can activate P2Y. Extracellular adenosine is re-cycled back into the cytoplasm via the nucleoside transporters (NT). (B) Pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) such as toxins, pathogens, metabolites, crystalline substances, nucleic acids, ion flux, reactive oxygen species, and ATP stimulate toll-like receptors (TLRs) and c type lectin receptors (CLRs) leading to activation of NF-κB followed by the subsequent transcriptional upregulation of NOD-like receptor family pyrin domain containing 3 (NLRP3) and pro-interleukin-1β. The cascade as depicted leads to the formation of gasdermin-D (GSDMD) and pyroptotic cell death through activation of caspase-4/5, capase-1, and GSDMD-NT along with release of ATP and other pro-inflammatory factors such as IL-1b, IL-18, and TFN-α.