SARS-CoV2 Decreases Human Beta-Defensin-1 and FoxI1 in the Oral Cavity Without Affecting CFTR

Abstract

Abstract The ionocyte is a newly characterized cell, first identified in the airway, that is hypothesized to play a role in innate immunity. Single cell RNA seq analysis showed that ionocytes (FoxI1 and CFTR-expressing cells) are also found in the oral cavity, and highly express human beta-defensin-1 (hBD-1). We showed that hBD-1 expression is upregulated by influenza, Herpes simplex virus and Sendai virus infection of monocytes and plasmacytoid dendritic cells but is downregulated in epithelial cells. The role of hBD1 in oral ionocytes in relation to SARS-CoV-2 infection is unknown. We tested the hypothesis that SARS-CoV2 virus modulates the expression of hBD-1, and this is associated with CFTR and FoxI1 expression in ionocytes in the oral cavity. Buccal swabs from patients with Covid19 and without Covid19 (recovered from Covid19 and non-Covid19) were analyzed for gene expression via quantitative RT-PCR of hBD-1, FoxI1, and CFTR. HBD-1 and FoxI1 mRNA levels (relative to beta-actin) were significantly decreased, but CFTR mRNA remained unchanged in the Covid19 patient cohort compared with the non-Covid19 and recovered patients. This supported the in vitro observation that enveloped viruses decrease hBD-1 in epithelial cells that make up most of the buccal swab sample. Immunohistochemistry on normal minor salivary gland sections revealed that FoxI1, CFTR and hBD-1 are all associated in proximity in the duct of the minor salivary gland. However, crosslinking studies, followed by Western blot analysis, indicated that hBD-1 and CFTR were not interacting. In conclusion, SARS-CoV2 modulates innate immunity in the oral cavity, as indicated by the decrease in hBD-1, and affects ionocytes, possibly affecting pH and osmolality in salivary glands. Research supported by a grant from NIH / NIDCR R01 DE031928 and the University of Louisville School of Dentistry Summer Research Scholar Program