Novel Association of Lyme disease, Age, and Atopic Dermatitis

Abstract

Abstract Borrelia burgdorferi is a bacterial spirochete that can cause Lyme disease (LD) after infecting a susceptible host. Immune responses to the bacteria are highly variable and host specific. The murine substrain, C3H/HeJ, is a frequently utilized model for LD. Interestingly, over a prolonged infection, mice develop dermatitis on tail skin, which shares critical features with human skin. Female C3H/HeJ mice aged 5–8 weeks, 1 year, or 2 years were infected intraperitoneally with 105 B. burgdorferi. Dermatitis was evaluated by gross examination and histology. Dermatitis worsened over the course of untreated infection, with ulceration, hemorrhaging, flaking, hair loss, and dark lesions as well as spongiosis and acanthosis. These features of dermatitis were present in infected mice after 1 year of age. This relationship among LD, atopic dermatitis, and host age seen in the C3H/HeJ mouse model is consistent with a large pool (342,499) of human epidemiological data from Finland. We identified 5,248 individuals with LD and 17,233 with atopic dermatitis in FinnGen. Retrospective analysis shows LD is associated with atopic dermatitis (OR = 1.91 [1.68 −2.37], P < 2e−16). More visits due to LD complications (3 or more visits versus 1 visit) were associated with atopic dermatitis (OR = 2.19 [1.35–3.55], P = 0.0014) and risk of developing atopic dermatitis over time (HR = 2.26 [1.54–3.95], P = 0.0017). Data from mice and humans reveal a novel relationship among LD, age, and atopic dermatitis. Through defined pathological scoring, we demonstrate the onset of murine atopic dermatitis with B. burgdorferi infection, which is further exacerbated by host age at time of infection, and likewise report a similar association in human epidemiological data from FinnGen. Research was supported by the Fairbairn Family foundation; Bay Area Lyme Foundation; the Younger family foundation; the Robert J. Kleberg, Jr., and Helen C. Kleberg Foundation; the Virginia and D. K. Ludwig Fund for Cancer Research; AML grant R01CA086017; the PCBC from NIHLB U01HL099999; as well as grant U19AI109662. M.C.T. was supported by Stanford Immunology training grant 5T32AI007290, and the NIH NRSA 1 F32 AI124558-01 award. L.B.T.D. was supported by a Stanford Diversifying Academia Recruiting Excellence fellowship. S.G. was supported by the California Institute for Regenerative Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.