W106 - The Impact of Age on Lyme Disease-associated Atopic Dermatitis

Sarah Galloway – Institute for Stem Cell Biology & Regenerative Medicine – Stanford University School of Medicine, Stanford, CA, USA; Maia Shoham – Institute for Stem Cell Biology & Regenerative Medicine – Stanford University School of Medicine, Stanford, CA, USA; Satu Strausz – Institute for Molecular Medicine Finland, Helsinki Institute of Life Science – University of Helsinki, Helsinki, Finland; Qingying Feng – Biological Engineering – MIT; Paige Hansen – Biological Engineering – MIT; Paul Mansfield – Institute for Stem Cell Biology & Regenerative Medicine – Stanford University School of Medicine, Stanford, CA, USA; FinnGen FinnGen; Laughing Torrez-Dulgeroff – Institute for Stem Cell Biology & Regenerative Medicine – Stanford University School of Medicine, Stanford, CA, USA; Atif Saleem – Pathology – Stanford University School of Medicine, Stanford, CA, USA; Eric Gars – Pathology – Stanford University School of Medicine, Stanford, CA, USA; Erin Sanders – Biological Engineering – MIT; Hanna Ollila – Institute for Molecular Medicine Finland, Helsinki Institute of Life Science – University of Helsinki, Helsinki, Finland; Irving Weissman – Institute for Stem Cell Biology & Regenerative Medicine – Stanford University School of Medicine, Stanford, CA, USA; Michal Tal – Biological Engineering – MIT

Abstract Text: Borrelia burgdorferi are bacteria that cause Lyme disease (LD) after infecting a susceptible host. Immune responses to the bacteria are highly variable and host specific, both in mice and humans. The murine substrain, C3H/HeJ, is a frequently utilized model for LD because it develops two key features of the human infection. The murine tail skin shares critical features with human skin, and could provide an important and underutilized tool to probe dermatological manifestations of the infection. Age and sex-matched C3H/HeJ mice aged 5-8 weeks, 1 year, or 2 years were infected with 105 B. burgdorferi for a minimum of 8 weeks, up to a maximum of 2 years. Features of the skin were evaluated by gross examination and histology. Key features of atopic dermatitis were present in infected mice after 1 year of age, including ulceration, hemorrhaging, flaking, hair loss, and dark lesions as well as spongiosis and acanthosis. Furthermore, mice infected with B. burgdorferi containing luciferase were istudied over a 6-month long time course using an In Vivo Imaging System, and were found to have significant infection in their tails. We then identified 5,248 individuals with LD and 17,233 with atopic dermatitis in FinnGen and find that also in human epidemiological data LD associates with atopic dermatitis (OR = 1.91 [1.68 -2.37], P < 2e-16). We demonstrate the onset of murine atopic dermatitis with LD, which is further exacerbated by host age at time of infection, and likewise report a similar association in humans.