| Abstract [eng] |
Macrophages are innate immune cells responsible for defence and homeostasis. One of the innate immunity defence mechanisms is inflammasome activation, which is also related to many inflammatory diseases. NLRP3 inflammasome can be triggered by a variety of factors. However, inflammasome activation by protein oligomers is less investigated. Our goal was to investigate macrophage activation by oligomeric proteins of various structures. We treated macrophages by these proteins: amyloid beta (Aβ) small oligomers and protofibrils; filamentous N proteins of paramyxoviruses; spherical virus-like particles (VLP) of polyomaviruses. We measured inflammatory cytokine secretion and NLRP3 inflammasome activation by assessing IL-1β secretion, caspase-1 activation and formation of ASC specks. We found that both Aβ structures activated inflammasome. This shows the probability that immune response arises before accumulation of Aβ fibrils during Alzheimer’s disease. Therefore, primary Aβ structures could be a source of neuroinflammation. Investigation of viral proteins showed that only VLP induced inflammatory response and activated inflammasome. VLP induced lysosomal damage and K+ ion efflux mediating inflammasome activation. Our investigation demonstrates that the structure of oligomeric proteins is one of the factors defining inflammatory response. Moreover, our results highlight NLRP3 inflammasome role in macrophage response to various molecular structures.Macrophages are innate immune cells responsible for defence and homeostasis. One of the innate immunity defence mechanisms is inflammasome activation, which is also related to many inflammatory diseases. NLRP3 inflammasome can be triggered by a variety of factors. However, inflammasome activation by protein oligomers is less investigated. Our goal was to investigate macrophage activation by oligomeric proteins of various structures. We treated macrophages by these proteins: amyloid beta (Aβ) small oligomers and protofibrils; filamentous N proteins of paramyxoviruses; spherical virus-like particles (VLP) of polyomaviruses. We measured inflammatory cytokine secretion and NLRP3 inflammasome activation by assessing IL-1β secretion, caspase-1 activation and formation of ASC specks. We found that both Aβ structures activated inflammasome. This shows the probability that immune response arises before accumulation of Aβ fibrils during Alzheimer’s disease. Therefore, primary Aβ structures could be a source of neuroinflammation. Investigation of viral proteins showed that only VLP induced inflammatory response and activated inflammasome. VLP induced lysosomal damage and K+ ion efflux mediating inflammasome activation. Our investigation demonstrates that the structure of oligomeric proteins is one of the factors defining inflammatory response. Moreover, our results highlight NLRP3 inflammasome role in macrophage response to various molecular structures. |
