The effector protein BPE005 from B. abortus induces collagen deposition and MMP-9 down-modulation via TGF-beta1 in hepatic stellate cells

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

INFECTION AND IMMUNITY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2015

0019-9567

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