Tu101 - Type 2 Immune Response and Lyme Disease: Can Allergic-type Responses to Bacteria Trigger Infection-induced Hypermobility?

Abstract Text: There are currently an estimated 476,000 cases of Lyme disease annually in the US, caused by the bacteria Borrelia burgdorferi (Bb). It is estimated that approximately 10% of people who have had Lyme disease go on to develop an infection-associated chronic illness, the underlying causes and long-term impacts of which remain poorly understood. In our Lyme disease mouse model, we discovered that C3H/HeJ mice mount significantly higher levels of anti-Bb IgE compared to C57BL/6 mice. As IgE is heavily involved in the Type II immune response, we further investigated the IgE epitopes and identified highly conserved epitopes that are conserved across spirochetes. Histological analysis of infected C3H mice also revealed IgE-dependent mast cell degranulation. Furthermore, we found that these mice develop atopic dermatitis (AD) on their tails, in sites with high levels of Bb load. Strikingly, we find that intradermal infection with Bb led to the development of AD followed by a gradual development of hypermobility in the tail, revealing infection-induced hypermobility which was not seen in uninfected age-matched C3H or age-matched B6 regardless of infection status. Moreover, we observed Bb in fresh mouse tissue under simultaneous label-free autoflourescent-multiharmonic microscopy in the connective tissues with extensive mast cell recruitment C3H mice suggesting that IgE-dependent mast cell-mediated connective tissue breakdown can result in infection-induced hypermobility.