This is a schematic diagram illustrating putative pathways for NAMP (nanomaterial-associated molecular patters)-induced NLRP3 inflammasome activation. Pathogen-associated molecular patterns (PAMPs) eg. lipopolysaccharides (LPS) are recognized by Toll-like receptors (TLRs) on the cell membrane, which leads to NF-κB activation and upregulation of pro-interleukin (IL)-1β and NLRP3 expression. High aspect radio nanomaterials (i.e. long multiwalled carbon nanotubes) are thought to trigger “frustrated phagocytosis” in macrophages, leading to NADPH oxidase (NOX1) activation, reactive oxygen species (ROS) generation and inflammasome activation. Smaller nanomaterials (i.e. short carbon nanotubes or silver nanoparticles of 28 nm), on the other hand, could be phagocytosed and once inside the cell induce lysosomal damage leading to release of cathepsins which cause mitochondrial damage and ROS production. In both cases, interaction of phagocytes with NAMPs induces an overproduction of ROS which results in assembly of NLRP3, ASC (apoptosis-associated speck-like protein containing a CARD), and pro-caspase-1 into the multimeric inflammasome complex, resulting in activation of caspase-1, and release of mature IL-1β, a key pro-inflammatory mediator. f72 d00 Lysosome innate immune response pathway PW:0000234 Pathway Ontology xenobiotic metabolic pathway PW:0001229 Pathway Ontology 25770769 PubMed It takes two to tango: Understanding the interactions between engineered nanomaterials and the immune system. Eur J Pharm Biopharm 2015 Farrera C Fadeel B nanomaterial response pathway PW:0001435 Pathway Ontology regulatory pathway PW:0000004 Pathway Ontology 23751779 PubMed Mechanisms of carbon nanotube-induced toxicity: focus on pulmonary inflammation. Adv Drug Deliv Rev 2013 Bhattacharya K Andón FT El-Sayed R Fadeel B macrophage CL:0000235 Cell Type