Uma revisão narrativa sobre a influencia do imunometabolismo na ativação dos inflamassomas em resposta ao toxoplasma gondii
Data
2022-12-19
Autores
Souza, Rafael Queiroz 
Orientadores
Bortoluci, Karina Ramalho
Tipo
Trabalho de conclusão de curso
Título da Revista
ISSN da Revista
Título de Volume
Resumo
A imunidade inata é a primeira linha de defesa do nosso organismo contra os patógenos e as células dessa imunidade possuem um repertório de receptores restritos a padrões moleculares. Esses receptores são capazes de reconhecer padrões moleculares associados a patógenos e a danos celulares. A família de receptores NLR constituem o maior grupo de receptores citoplasmáticos e podem formar estruturas denominadas inflamassomas. Os inflamassomas são complexos multiproteicos capazes de ativar a caspase-1 e montar uma resposta inflamatória. Um processo muito importante decorrente da ativação da caspase 1 é a morte celular denominada piroptose e a clivagem das citocinas pró inflamatórias IL-1β e IL-18. Já é estabelecido pela literatura que as vias metabólicas e o metabolismo celular são de extrema importância no estudo da imunologia e estão intrinsecamente ligados com as respostas das células do sistema imune. O itaconato é um metabólito importante no contexto inflamatório, com grande efetividade no controle bacteriano , e um dos mecanismos que possibilita essa ação antimicrobiana é a sua ação inibitória sobre a enzima isocitrato liase bacteriana. Outro metabólito de importância no contexto imunológico é o fumarato. Foi observado que o dimetil fumarato (DMF) e o fumarato endógeno são capazes de reagir com a gasdermina D (GSDMD), molécula efetora da piroptose, inibindo esse processo. Um componente celular de grande importância quando falamos de uma resposta imunológica é a mitocôndria, pois desempenha um papel central na regulação de vias de receptores da imunidade inata. O Toxoplasma gondii é um protozoário do filo Apicomplexa que é capaz de subverter o sistema imune inato do hospedeiro pois recruta mitocôndrias do mesmo para o vacúolo parasitóforo. Assim, o objetivo desse trabalho é entender a influência do metabolismo de células imunes na ativação dos inflamassomas durante a infecção pelo T. gondii por meio da revisão de artigos disponíveis em bases dados. Esse entendimento é de grande importância para o campo pois trará embasamento e questões relevantes a serem abordadas em pesquisas futuras.
Innate immunity is the first line of defense against pathogens, and the innate immune cells possess a repertory of receptors that are restricted to molecular patterns. These receptors can recognize pathogens- or damage-associated molecular patterns. The NLR receptors family constitutes the largest group of cytoplasmic receptors and can form structures called inflammasomes. Inflammasomes are multiprotein complexes capable of activating caspase-1 and assembling an inflammatory response. Caspase-1 activation leads to cell death by pyroptosis and cleavage of IL-1b and IL-18 pro-inflammatory cytokines. It is already established in the literature that metabolic pathways and cell metabolism are intrinsically related to immune system cell responses. Itaconate is an important metabolite in the inflammatory context, with great effectiveness in the bacterial control, through its inhibitory effect on the bacterial enzyme isocitrate lyase. Another important metabolite in the immunological context is fumarate. It has been observed that dimethyl fumarate (DMF) and endogenous fumarate interact with gasdermin D (GSDMD), effector molecule of pyroptosis, thereby inhibiting this process. A cellular component of great importance for the immune response are the mitochondria, through their critical role in regulating innate immunity receptors. Toxoplasma gondii is an Apicomplexa protozoan able to subvert the host’s innate immune system since it recruits their mitochondria into the parasitophorous vacuole. Therefore, the objective of this project is to understand the influence of immune cell metabolism on inflammasome activation during T. gondii infection through revision of articles available in databases. Understanding this subject is of great importance to the field since it will bring basis and relevant questions to be addressed in future research.
Innate immunity is the first line of defense against pathogens, and the innate immune cells possess a repertory of receptors that are restricted to molecular patterns. These receptors can recognize pathogens- or damage-associated molecular patterns. The NLR receptors family constitutes the largest group of cytoplasmic receptors and can form structures called inflammasomes. Inflammasomes are multiprotein complexes capable of activating caspase-1 and assembling an inflammatory response. Caspase-1 activation leads to cell death by pyroptosis and cleavage of IL-1b and IL-18 pro-inflammatory cytokines. It is already established in the literature that metabolic pathways and cell metabolism are intrinsically related to immune system cell responses. Itaconate is an important metabolite in the inflammatory context, with great effectiveness in the bacterial control, through its inhibitory effect on the bacterial enzyme isocitrate lyase. Another important metabolite in the immunological context is fumarate. It has been observed that dimethyl fumarate (DMF) and endogenous fumarate interact with gasdermin D (GSDMD), effector molecule of pyroptosis, thereby inhibiting this process. A cellular component of great importance for the immune response are the mitochondria, through their critical role in regulating innate immunity receptors. Toxoplasma gondii is an Apicomplexa protozoan able to subvert the host’s innate immune system since it recruits their mitochondria into the parasitophorous vacuole. Therefore, the objective of this project is to understand the influence of immune cell metabolism on inflammasome activation during T. gondii infection through revision of articles available in databases. Understanding this subject is of great importance to the field since it will bring basis and relevant questions to be addressed in future research.