TLR7 and TLR3 SenseBrucella abortusRNA to Induce Proinflammatory Cytokine Production but They Are Dispensable for Host Control of Infection.
Brucella abortusis a Gram-negative, facultative intracellular bacterium that causes brucellosis, a worldwide zoonotic disease leading to undulant fever in humans and abortion in cattle. The immune response against this bacterium relies on the recognition of microbial pathogen-associated molecular patterns, such as lipoproteins, lipopolysaccharides, and DNA; however, the immunostimulatory potential ofB. abortusRNA remains to be elucidated. Here, we show that dendritic cells (DCs) produce significant amounts of IL-12, IL-6, and IP-10/CXCL10, when stimulated with purifiedB. abortusRNA. IL-12 secretion by DCs stimulated with RNA depends on TLR7 while IL-6 depends on TLR7 and partially on TLR3. Further, only TLR7 plays a role in IL-12 production induced byB. abortusinfection. Moreover, cytokine production in DCs infected withB. abortusor stimulated with bacterial RNA was reduced upon pretreatment with MAPK/NF-κB inhibitors. By confocal microscopy, we demonstrated that TLR7 is colocalized withB. abortusin LAMP-1+Brucella-containing vacuoles. Additionally, type I IFN expression and IP-10/CXCL10 secretion in DCs stimulated with bacterial RNA were dependent on TLR3 and TLR7. Our results suggest that TLR3 and TLR7 are not required to controlBrucellainfectionin vivo, but they play an important role on sensingB. abortusRNAin vitro.
Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte , Brazil.
Priscila C
PC
Campos
Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte , Brazil.
Marco Túlio R
MT
Gomes
Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte , Brazil.
Erika S
ES
Guimarães
Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte , Brazil.
Gabriela
G
Guimarães
Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), Conselho Nacional de Desenvolvimento Científico e Tecnológico, Ministério de Ciência Tecnologia e Inovação, Salvador, Brazil.
Sergio C
SC
Oliveira
B. abortus; RNA; cytokines; innate immunity; toll-like receptors; type I IFN