Novosphingobium aromaticivorans - causative agent or trigger of Primary Biliary Cirrhosis? (130.29)

Abstract

Abstract Undetected bacterial infections elicit strong immune responses that can masquerade into autoimmune diseases. This has recently been proposed for Primary Biliary Cirrhosis (PBC), a liver disease where individuals have signs of chronic immune responses against Novosphingobium aromaticivorans, an ubiquitous xenobiotic-metabolizing microorganism. Humans with PBC exhibit also NKT cell redistribution to the liver. We have obtained evidence that infection of female B6, SJL and NOD congenic mice with Novosphingobium triggers potent and persistent IgG responses to the mitochondrial antigens of PBC and induce biliary duct lesions and portal inflammation resembling PBC in humans. As our previous work has identified microbial glycosphingolipid (GSL) ligands in the cell wall of these Novosphingobium bacteria that trigger NKT cell activation we propose that the striking differences originate from the nature of the innate signals associated with Sphingomonas infection, which recruits NKT cell help for autoreactive B cells, as opposed to TLR signaling alone in the case of other bacteria, which fails to provide similar helper signals.