TY - JOUR
T1 - Brucella abortus nitric oxide metabolite regulates inflammasome activation and IL-1β secretion in murine macrophages
AU - Campos, Priscila Carneiro
AU - Gomes, Marco Túlio Ribeiro
AU - Marinho, Fábio Antônio Vitarelli
AU - Guimarães, Erika Sousa
AU - de Moura Lodi Cruz, Mariza Gabriela Faleiro
AU - Oliveira, Sergio Costa
N1 - Funding Information:
The authors thank Dr. Xavier de Bolle (University of Namur, Belgium) for providing the pSKoriT:narGKanR plasmid. The authors also thank Dra. Leda Quércia Vieira (Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil) for providing the iNOS and gp9phox KO mice, and Dr. José Carlos Farias Alves Filho (Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil) for providing P2X7R KO mice. This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (grants 406883/2018-1, 402527/2013-5, and 302660/2015-1), Fundação de Amparo à Pesquisa do Estado de Minas Gerais (grants APQ 837/15 and APQ 1945/17), Rede Mineira de Imunobiológicos (grant 00140-16), and National Institute of Health (R01 AI116453).
Funding Information:
Acknowledgements: The authors thank Dr. Xavier de Bolle (University of Namur, Belgium) for providing the pSKoriT:narGKanR plasmid. The authors also thank Dra. Leda Quércia Vieira (Insti-tuto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil) for providing the iNOS and gp9phox KO mice, and Dr. JoséCarlos Farias Alves Filho (Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil) for providing P2X7R KO mice. This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (grants 406883/2018-1, 402527/2013-5, and 302660/2015-1), Funda¸cão de Amparo à Pesquisa do Estado de Minas Gerais (grants APQ 837/15 and APQ 1945/17), Rede Mineira de Imunobiológicos (grant 00140-16), and National Institute of Health (R01 AI116453).
Publisher Copyright:
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2019/7
Y1 - 2019/7
N2 - NLRP3 inflammasome is a protein complex crucial to caspase-1 activation and IL-1β and IL-18 maturation. This receptor participates in innate immune responses to different pathogens, including the bacteria of genus Brucella. Our group recently demonstrated that Brucella abortus-induced IL-1β secretion involves NLRP3 inflammasome and it is partially dependent on mitochondrial ROS production. However, other factors could be involved, such as P2X7-dependent potassium efflux, membrane destabilization, and cathepsin release. Moreover, there is increasing evidence that nitric oxide acts as a modulator of NLRP3 inflammasome. The aim of this study was to unravel the mechanism of NLRP3 inflammasome activation induced by B. abortus, as well as the involvement of bacterial nitric oxide (NO) as a modulator of this inflammasome pathway. We demonstrated that NO produced by B. abortus can be used by the bacteria to modulate IL-1β secretion in infected murine macrophages. Additionally, our results suggest that B. abortus-induced IL-1β secretion depends on a P2X7-independent potassium efflux, lysosomal acidification, cathepsin release, mechanisms clearly associated to NLRP3 inflammasome. In summary, our results help to elucidate the molecular mechanisms of NLRP3 activation and regulation during an intracellular bacterial infection.
AB - NLRP3 inflammasome is a protein complex crucial to caspase-1 activation and IL-1β and IL-18 maturation. This receptor participates in innate immune responses to different pathogens, including the bacteria of genus Brucella. Our group recently demonstrated that Brucella abortus-induced IL-1β secretion involves NLRP3 inflammasome and it is partially dependent on mitochondrial ROS production. However, other factors could be involved, such as P2X7-dependent potassium efflux, membrane destabilization, and cathepsin release. Moreover, there is increasing evidence that nitric oxide acts as a modulator of NLRP3 inflammasome. The aim of this study was to unravel the mechanism of NLRP3 inflammasome activation induced by B. abortus, as well as the involvement of bacterial nitric oxide (NO) as a modulator of this inflammasome pathway. We demonstrated that NO produced by B. abortus can be used by the bacteria to modulate IL-1β secretion in infected murine macrophages. Additionally, our results suggest that B. abortus-induced IL-1β secretion depends on a P2X7-independent potassium efflux, lysosomal acidification, cathepsin release, mechanisms clearly associated to NLRP3 inflammasome. In summary, our results help to elucidate the molecular mechanisms of NLRP3 activation and regulation during an intracellular bacterial infection.
KW - Brucella abortus
KW - NLRP3 inflammasome
KW - immune evasion
KW - nitric oxide
KW - ΔnarG mutant
UR - http://www.scopus.com/inward/record.url?scp=85063807819&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85063807819&partnerID=8YFLogxK
U2 - 10.1002/eji.201848016
DO - 10.1002/eji.201848016
M3 - Article
C2 - 30919410
AN - SCOPUS:85063807819
SN - 0014-2980
VL - 49
SP - 1023
EP - 1037
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 7
ER -