Type 4 secretion system (T4SS) and the secreted protein BPE005 from Brucella abortus modulates hepatic stellate cells responses.

ARRIOLA BENITEZ P. C., PESCE VIGLIETTI A. I., REY SERANTES D., HERRMANN C. K., VANZULLI S., COMERCI D. J. GIAMBARTOLOMEI G. H., DELPINO M. V.

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Inmunología.; 2015

The liver isaffected in human brucellosis. Hepatic stellate cells (HSC) are the major cellsinvolved in liver fibrosis, and they are the resident antigen-presenting cells.Brucella abortus (Ba) could beinvolved in the modulation of immune response in liver through activation ofinflammasome with concomitant fibrosis to repair the damage. Ba tilts HSC to a profibrogenic phenotype in a way that involves afunctional T4SS and the secreted protein BPE005. Todetermine in vivo relevance of the role of BPE005 in liver fibrosis, BALB/c mice were infected with Ba and bpe005 mutant. Masson's trichrome(p<0.05) and Sirius red (p<0.01) staining revealed that the presence of fibrotic patches was lower in miceinfected with Ba bpe005 mutant than in those infected with Ba.TGF-β1 secretion was lower in livers from Ba bpe005mutant-infected mice than those infected with Ba (p<0.05), and HSC are the main cells involved in TGF-β1secretion as was revealed by immunohistochemistry. HSC could expressinflammasomes, our results using LX-2 cell line indicated that Ba inducethe secretion of IL-1β in a mechanism dependent on the presence of a functionalT4SS but not the BPE005 protein (p<0.001). Experiments conducted todetermine if Ba could modulate LX-2 cells antigen presenting cells,revealed that Ba infection induced MHC-I (p<0.01) and MHC-II (p<0.001)expression, but not affect the expression of (CD40, CD80 and CD86) in LX-2. These results indicate that the T4SS and BPE005 are involved in most of themechanisms involved in the modulation of liver responses.