AUTHOR=Campos Priscila C. , Gomes Marco Túlio R. , Guimarães Erika S. , Guimarães Gabriela , Oliveira Sergio C. 

TITLE=TLR7 and TLR3 Sense Brucella abortus RNA to Induce Proinflammatory Cytokine Production but They Are Dispensable for Host Control of Infection

JOURNAL=Frontiers in Immunology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.00028

DOI=10.3389/fimmu.2017.00028

ISSN=1664-3224

ABSTRACT=<p><italic>Brucella abortus</italic> is 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 of <italic>B. abortus</italic> RNA 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 purified <italic>B. abortus</italic> RNA. 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 by <italic>B. abortus</italic> infection. Moreover, cytokine production in DCs infected with <italic>B. abortus</italic> or stimulated with bacterial RNA was reduced upon pretreatment with MAPK/NF-κB inhibitors. By confocal microscopy, we demonstrated that TLR7 is colocalized with <italic>B. abortus</italic> in LAMP-1<sup>+</sup><italic>Brucella</italic>-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 control <italic>Brucella</italic> infection <italic>in vivo</italic>, but they play an important role on sensing <italic>B. abortus</italic> RNA <italic>in vitro</italic>.</p>