Category: Immunity & infection
The role of CD47 in the battlefield of Borrelia-host immune modulation in Lyme disease
Michal Caspi Tal, Maia Shoham, Balyn Zaro, Maxim Markovic, Irving Weissman
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine
CD47 is a broadly expressed cell surface molecule that transmits a (“don’t eat me”) phagocytic inhibitory signal via the SIRPα receptor on macrophages. CD47 blockade in cancer therapy has received a lot of attention, but few studies have investigated the role of CD47 in infectious disease. We find that CD47 upregulation occurs during a broad range of viral and bacterial infections, and is part of the host response to pathogen recognition. Furthermore, SIRPα, the receptor for CD47 is a highly polymorphic immune protein. As all Poxviruses encode their own CD47 mimic, it has been postulated that SIRPα has been under positive selection to distinguish host and mimic CD47. We found and characterized additional CD47 mimic proteins encoded by bacteria and fungal pathogens which can modulate immune responses. Correspondingly, we identified critical SIRPα polymorphisms that have been under balancing selection which impact SIRPα expression levels and responsiveness. The CD47 mimic protein encoded by the bacterial pathogen, Borrelia burgdorferi (Bb), that causes Lyme disease can skew immune responses from protective to pathological. We are characterizing the immunomodulatory mechanisms employed by Bb in order to understand how this differentially impacts a polymorphic population. We hope that this will enable targeted treatment of very diverse symptomatic presentations of Lyme disease.