SARS-CoV-2 infection of salivary glands Compromises the production of a secreted antifungal peptide with potential implications for Development of oral candidiasis.

Publication date: Dec 12, 2024

Saliva contains antimicrobial peptides considered integral components of host innate immunity, and crucial for protection against colonizing microbial species. Most notable is histatin-5 which is exclusively produced in salivary glands with uniquely potent antifungal activity against the opportunistic pathogen Candida albicans. Recently, SARS-CoV-2 was shown to replicate in salivary gland acinar cells eliciting local immune cell activation. In this study, we performed studies to investigate the implications of SARS-CoV-2 infection on salivary histatin-5 production and Candida colonization. Bulk RNA-sequencing of parotid salivary glands from COVID-19 autopsies demonstrated statistically significant decreased expression of histatin and amylase genes. In situ hybridization, coupled with immunofluorescence for co-localization of SARS-CoV-2 spike and histatin in salivary gland cells, showed that histatin was absent or minimally present in acinar cells with replicating viruses. To investigate the clinical implications of these findings, salivary histatin-5 levels and oral Candida burden in saliva samples from three independent cohorts of mild and severe COVID-19 patients and matched healthy controls were evaluated. Results revealed significantly reduced histatin-5 in SARS-CoV-2 infected subjects, concomitant with enhanced prevalence of C. albicans. Analysis of prospectively recovered samples indicated that the decrease in histatin-5 is likely reversible in mild-moderate disease as concentrations tended to increase during the post-acute phase. Importantly, salivary cytokine profiling demonstrated correlations between activation of the Th17 inflammatory pathway, changes in histatin-5 concentrations, and subsequent clearance of C. albicans in a heavily colonized subject. The importance of salivary histatin-5 in controlling the proliferation of C. albicans was demonstrated using an ex vivo assay where C. albicans was able to proliferate in COVID-19 saliva with low histatin-5, but not with high histatin-5. Taken together, the findings from this study potentially implicate SARS-CoV-2 infection of salivary glands with compromised oral innate immunity, and potential predisposition to oral candidiasis.

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Concepts Keywords
Amylase Albicans
Host Antifungal
Immunofluorescence Candida
Saliva Cov
Th17 Covid
Demonstrated
Glands
Histatin
Implications
Infection
Oral
Production
Saliva
Salivary
Sars

Semantics

Type Source Name
disease MESH SARS-CoV-2 infection
pathway REACTOME SARS-CoV-2 Infection
disease IDO production
disease MESH oral candidiasis
pathway REACTOME Antimicrobial peptides
disease IDO host
disease IDO opportunistic pathogen
disease IDO assay
disease MESH Allergy
disease MESH Infectious Diseases
disease MESH inflammation
disease IDO pathogen
disease IDO commensal
disease IDO replication
disease MESH infections
disease MESH opportunistic infections

Original Article

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