The Dp16 Down syndrome mouse model does not exhibit oral interferon-gammopathy or susceptibility to oral candidiasis

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Abstract
Down syndrome, or Trisomy 21, is associated with excessive interferon (IFN) signaling and concomitant susceptibility to both autoimmunity and immunodeficiency. One of the many clinical phenotypes observed in people with Down syndrome is increased risk for oral candidiasis. Because oral candidiasis can be caused by excessive IFN-γ signaling, we asked whether IFN-gammopathy could be playing a role in susceptibility to oral candidiasis in Down syndrome. We used the Dp16 mouse model of Down syndrome, which displays mild systemic interferonopathy, to model oral candidiasis. We found that the Dp16 model does not exhibit oral IFN-gammopathy and is not susceptible to oral candidiasis. We exposed the Dp16 mice to various inflammatory and infectious stimuli with the goal to induce enhanced local IFN-γ responses, but these did not induce oral IFN-gammopathy or promote susceptibility to oral candidiasis. We conclude that the Dp16 model is not well-suited to study oral IFN-gammopathy or oral candidiasis. Clinical studies of oral candidiasis in people with Down syndrome are warranted. IMPORTANCE: Down syndrome, caused by three copies of chromosome 21, presents with different medical conditions in different people. One such condition for some people with Down syndrome is increased susceptibility to oral infection with the fungus Candida albicans. C. albicans is a normal member of the human oral microbiome, but it can also cause painful infections. Down syndrome causes an excess of inflammatory molecules called interferons (IFNs). Excessive inflammation due to one type of IFN, IFN-γ, can cause susceptibility to oral C. albicans infection in certain settings. Thus, we wanted to assess whether excessive IFNs may cause susceptibility to oral C. albicans infection in Down syndrome. We used the Dp16 mouse model of Down syndrome. We found, however, that Dp16 mice did not exhibit excessive IFN-γ oral mucosal responses and were not susceptible to oral C. albicans and thus are not a suitable model for studying this phenomenon.
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  • Division of Intramural Research

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