The effector protein BPE005 from B. abortus induces collagen deposition and MMP-9 down-modulation via TGF-β1 in hepatic stellate cells.

PAULA CONSTANZA ARRIOLA BENITEZ; DIEGO REY SERANTES; CLAUDIA KARINA HERRMANN; AYELÉN IVANA PESCE VIGLIETTI; SILVIA VANZULLI; GUILLERMO HERNÁN GIAMBARTOLOMEI; DIEGO JOSÉ COMERCI ; MARÍA VICTORIA DELPINO

INFECTION AND IMMUNITY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2016

0019-9567

The liveris frequently affected in patients with active brucellosis. In the presentstudy, we identified a virulence factor involved in the modulation of hepaticstellate cell function and consequent fibrosis during Brucella abortusinfection. This study assessed the role of BPE005 protein from B. abortus inthe fibrotic phenotype induced on hepatic stellate cells during B. abortusinfection in vitro and in vivo. We demonstrated that the fibrotic phenotypeinduced by B. abortus on hepatic stellate (LX-2) cells was dependent on BPE005,a protein associated with the type IV secretion system (T4SS) VirB from B.abortus. Our results indicated that B. abortus inhibits matrixmetalloproteinase 9 (MMP-9) secretion through the activity of theBPE005-secreted protein and induces concomitant collagen deposition by LX-2cells. BPE005 is a small protein containing a cyclic nucleotide monophosphate bindingdomain (cNMP) that modulates the LX-2 cell phenotype through a mechanism thatis dependent on the cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway.Altogether, these results indicate that B. abortus tilts LX-2 cells to aprofibrogenic phenotype employing a functional T4SS and the secreted BPE005protein through a mechanism that involves the cAMP and PKA signaling pathway