Endodontic Resident Boston University Boston, Massachusetts
Disclosure(s): No financial relationships to disclose
In disseminating endodontic infections (DEI), sexual dimorphism has been observed where male but not female mice mildly immunosuppressed by blockade of IL-1 signaling, and challenged with an endodontic infection, developed facial abscesses, weight loss, splenomegaly, and sepsis, which was often fatal. The central hypothesis is that estrogen increases the numbers and function of N1 neutrophils, resulting in effective anti- microbial immunity to DEI, whereas androgens are inhibitory. There are two aims in this study: Aim 1 is to determine the efficacy of sex hormone modulation of neutrophil-mediated resistance to DEI and sepsis. Aim 2 is to determine the effect of hormonal interventions on neutrophil polarization and function. The therapeutic effects of estrogen and the androgen receptor antagonist enzalutamide (ENZ) on DEI will be evaluated in the adult male group through direct observation of facial abscess formation, survival rate, and daily weight. Male mice sub-groups will be categorized by hormonal treatment. Neutrophil anti-microbial activities and systemic bacterial load will be quantified through spleen samples after mice expire or after 21 days. Periapical granulomas will be characterized by RNA sequencing to determine neutrophil distribution. Results indicated that immunocompromised IL-1R1 Knock Out mice with no hormonal intervention were most susceptible to DEI and those treated with estrogen were protected. We expect that N1 neutrophils will predominate in granulomas and mice that are protected by hormone modulation, whereas N2 will be increased in susceptible mice. Survival rate, abscess formation, and weights will be logged and trends will be analyzed/presented in a trend chart format.
