• Impaired Histatin-5 Levels and Salivary Antimicrobial Activity against C. albicans in HIV Infected Individuals

      Al Thunayyan, Awdah Anwar; Jabra-Rizk, Mary Ann (2013)
      HIV-infected individuals constitute a population highly susceptible to opportunistic infections particularly oral candidiasis (OC) caused by the most pathogenic human fungal species Candida albicans. The susceptibility to OC is enhanced under reduced CD4+ T-cells however local host defenses may also play a key role. Host-produced salivary antimicrobial peptides are considered to be an important part of the host innate immune system involved in protection of the oral cavity against colonization and infection by microbial species. Histatin-5 (Hst-5) specifically has exhibited potent anti-candidal properties in vitro. However, its importance in protecting the oral mucosa against candidal colonization and importantly, its contribution to the observed enhanced susceptibility of HIV+ individuals to candidiasis has not been previously investigated most likely due to the lack of feasible and sensitive methods for measuring salivary Hst-5 concentrations. To that end, the goal of this study was to develop a novel immunoassay to accurately measure and analyze salivary Hst-5 levels within the context of HIV infection and oral candidal colonization in order to validate the hypothesis that salivary Hst-5 levels are compromised in HIV+ individuals. The results from these studies demonstrated that salivary Hst-5 levels are significantly (60%) decreased in HIV+ individuals compared to healthy subjects concomitant with enhanced candidal prevalence. The findings generated from this project provided new insights into oral innate immune defense mechanisms and the enhanced susceptibility of HIV+ individuals to oral candidiasis.
    • Long-Term Post-COVID-19 Associated Oral Inflammatory Sequelae

      Alfaifi, Areej; Sultan, Ahmed S.; Montelongo-Jauregui, Daniel; Meiller, Timothy F.; Jabra-Rizk, Mary Ann (2022-03-04)
      The oral cavity remains an underappreciated site for SARS-CoV-2 infection despite the myriad oral conditions observed in COVID-19 patients. Recently, replicating SARS-CoV-2 was found inside salivary epithelial cells resulting in inflammation and atrophy of salivary glands. Saliva possesses healing properties crucial for maintaining the health of the oral mucosa. Specifically, salivary antimicrobial peptides, most notable, histatin-5 exclusively produced in salivary glands, plays a vital role in innate immunity against colonizing microbial species. The demonstration of SARS-CoV-2 destruction of gland tissue where histatin-5 is produced strongly indicate that histatin-5 production is compromised due to COVID-19. Here we present a case of a patient presenting with the patient and matched healthy subject for histatin-5 and key cytokines. Findings demonstrated significantly reduced histatin-5 levels in patient’s saliva and activation of the Th17 inflammatory pathway. As histatin-5 exhibits potent activity against the opportunistic oral pathogen Candida albicans, we evaluated saliva potency against C. albicans ex vivo. Compared to control, patient saliva exhibited significantly reduced anti-candidal efficacy. Although speculative, based on history and salivary analysis we hypothesize that salivary histatin-5 production may be compromised due to SARS-CoV-2 mediated salivary gland destruction. With the current lack of emphasis on implications of COVID-19 on oral health, this report may provide lacking mechanistic insights that may lead to reassessment of risks for oral opportunistic infections and mucosal inflammatory processes in acutely-ill and recovered COVID-19 patients.