title: The role of NLRP3 and AIM2 in inflammasome activation during Brucella abortus infection.
abstract: The innate immune system is essential for the detection and elimination of bacterial pathogens. Upon inflammasome activation, caspase-1 cleaves pro-IL-1β and pro-IL-18 to their mature forms IL-1β and IL-18, respectively, and the cell undergoes inflammatory death termed pyroptosis. Here, we reviewed recent findings demonstrating that Brucella abortus ligands activate NLRP3 and AIM2 inflammasomes which lead to control of infection. This protective effect is due to the inflammatory response caused by IL-1β and IL-18 rather than cell death. Brucella DNA is sensed by AIM2 and bacteria-induced mitochondrial reactive oxygen species is detected by NLRP3. However, deregulation of pro-inflammatory cytokine production can lead to immunopathology. Nervous system invasion by bacteria of the genus Brucella results in an inflammatory disorder termed neurobrucellosis. Herein, we discuss the mechanism of caspase-1 activation and IL-1β secretion in glial cells infected with B. abortus. Our results demonstrate that the ASC inflammasome is indispensable for inducing the activation of caspase-1 and secretion of IL-1β upon infection of astrocytes and microglia with Brucella. Moreover, our results demonstrate that secretion of IL-1β by Brucella-infected glial cells depends on NLRP3 and AIM2 and leads to neurobrucellosis. Further, the inhibition of the host cell inflammasome as an immune evasion strategy has been described for bacterial pathogens. We discuss here that the bacterial type IV secretion system VirB is required for inflammasome activation in host cells during infection. Taken together, our results indicate that Brucella is sensed by ASC inflammasomes mainly NLRP3 and AIM2 that collectively orchestrate a robust caspase-1 activation and pro-inflammatory response.
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte- Minas Gerais, Brazil.
authors.forename: Fernanda M
authors.initials: FM
authors.lastname: Marim
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte- Minas Gerais, Brazil.
authors.forename: Miriam M Costa
authors.initials: MMC
authors.lastname: Franco
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte- Minas Gerais, Brazil.|Programa de Pós-Graduação em Genética, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte- Minas Gerais, Brazil.
authors.forename: Marco Tulio R
authors.initials: MTR
authors.lastname: Gomes
authors.affiliation: Instituto de Inmunología, Genética y Metabolismo (CONICET/UBA), Hospital de Clínicas "José de San Martín", Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires.
authors.forename: Maria Cruz
authors.initials: MC
authors.lastname: Miraglia
authors.affiliation: Instituto de Inmunología, Genética y Metabolismo (CONICET/UBA), Hospital de Clínicas "José de San Martín", Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires.
authors.forename: Guillermo H
authors.initials: GH
authors.lastname: Giambartolomei
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte- Minas Gerais, Brazil.
authors.forename: Sergio C
authors.initials: SC
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D002003:Brucella abortus / Q000276:immunology*; D002006:Brucellosis / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism; D004269:DNA, Bacterial / Q000276:immunology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*
chemical_list: C410167:AIM2 protein, human; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein
keywords: AIM2; Brucella; Dendritic cells; Inflammasome; NLRP3; Neurobrucellosis