Borrelia burgdorferi is the causative agent of Lyme disease, the most common vector-transmitted disease in the United States. Untreated, Borrelia can persist in the joints in spite of a robust immune response. Our laboratory is interested in the mechanisms by which the spirochete can evade the immune system. We have previously shown that chondrocytes upregulate matrix metalloproteases (MMPs) in response to infection. MMPs are proteases that degrade extracellular matrices and have been implicated in other diseases such as rheumatoid arthritis. It is not known how increased MMP production benefits the bacteria; however, we hypothesize that these MMPs may play a role in Borrelia immune evasion. Chemokines are potent activators of the innate system which act by directing monocytes and other phagocytic cells to the site of infection. Recently, MMPs have been shown to degrade chemokines rendering them inactive and incapable of coordinating immune cells. This application will test whether MMPs produced by chondrocytes cleave chemokines thereby creating a protected niche for Borrelia to survive and persist even in the presence of an acute host inflammatory response. ? ? ?
| Heilpern, Andrew J; Wertheim, Warren; He, Jia et al. (2009) Matrix metalloproteinase 9 plays a key role in lyme arthritis but not in dissemination of Borrelia burgdorferi. Infect Immun 77:2643-9 |
