title: NLRP12 negatively regulates proinflammatory cytokine production and host defense against Brucella abortus.
abstract: Brucella abortus is the causative agent of brucellosis, which causes abortion in domestic animals and undulant fever in humans. This bacterium infects and proliferates mainly in macrophages and dendritic cells, where it is recognized by pattern recognition receptors (PRRs) including Nod-like receptors (NLRs). Our group recently demonstrated the role of AIM2 and NLRP3 in Brucella recognition. Here, we investigated the participation of NLRP12 in innate immune response to B. abortus. We show that NLRP12 inhibits the early production of IL-12 by bone marrow-derived macrophages upon B. abortus infection. We also observed that NLRP12 suppresses in vitro NF-κB and MAPK signaling in response to Brucella. Moreover, we show that NLRP12 modulates caspase-1 activation and IL-1β secretion in B. abortus infected-macrophages. Furthermore, we show that mice lacking NLRP12 are more resistant in the early stages of B. abortus infection: NLRP12-/-infected-mice have reduced bacterial burdens in the spleens and increased production of IFN-γ and IL-1β compared with wild-type controls. In addition, NLRP12 deficiency leads to reduction in granuloma number and size in mouse livers. Altogether, our findings suggest that NLRP12 plays an important role in negatively regulating the early inflammatory responses against B. abortus.
authors: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors: Tatiana N
authors: TN
authors: Silveira
authors: 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: Marco Túlio R
authors: MT
authors: Gomes
authors: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors: Luciana S
authors: LS
authors: Oliveira
authors: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors: Priscila C
authors: PC
authors: Campos
authors: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors: Gabriela G
authors: GG
authors: Machado
authors: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors: Sergio C
authors: SC
authors: Oliveira
mesh_terms: D000818:Animals; D002003:Brucella abortus / Q000276:immunology*; D002006:Brucellosis / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D020170:Caspase 1 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D006099:Granuloma / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate; D058847:Inflammasomes; D018836:Inflammation Mediators / Q000378:metabolism*; D018664:Interleukin-12 / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D058847:Inflammasomes; D018836:Inflammation Mediators; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; C553199:NLRP12 protein, mouse; D018664:Interleukin-12; D020928:Mitogen-Activated Protein Kinases; D020170:Caspase 1
keywords: Brucella abortus; Inflammasome; Macrophage; NLRP12; Nod-like receptors