Deer tick secretes serpins 7A and 32A to modulate host defense pathways: Hemostasis and inflammation; facilitating Borrelia burgdorferi transmission and dissemination

For decades, ticks and tick-borne diseases (TBDs) have had a detrimental impact on public and veterinary health. Lyme disease (LD), caused by Borrelia burgdorferi (Bb) or B. mayonii that are transmitted by Ixodes spp ticks accounts for more than 65% of TBD cases. Immunization against tick feeding using tick-antigen based vaccines seem to be a promising route toward prevention of human TBD. The limitation toward global adoption of tick-antigen based vaccines to prevent human TBD is the lack of effective antigens. There is evidence showing that serine protease inhibitors (serpins) in tick saliva may protect transmitted Bb from the host’s innate immune responses and could therefore be potential antigen targets for tick vaccine development. We have previously determined proteins that Bb infected I. scapularis inject into the host during feeding. Here we have characterized two serine protease inhibitors (serpins) that were enhanced by Bb infection. Consistent findings that serpins regulated host defense pathways (eg. Inflammation and blood clotting) two serpins (S)7A and 32A likely modulate host defense to allow feeding and transmission of Bb.  We show that S7A, is a strong inhibitor of trypsin and blood clotting system proteases, Factors IX, X, and XI. Likewise, S32A, is a strong inhibitor of pro-inflammatory proteases, Chymase (in vitro and in vivo) and Cathepsin G, which are secreted by two of the first cells that infiltrate the feeding site: mast cells and neutrophils. We are investigating the role of these serpins in Bb transmission and dissemination.