Biology subjects

Nares, S.

Publications and source records attributed to Nares, S..

3 recordsLinked to original sources

bioRxiv2025

Oral Cavity Serves as Long-Term COVID-19 Reservoir with Increased Periodontal and Viral Disease Risk

BackgroundSARS-CoV-2 infection can lead to long-term health problems affecting multiple body systems termed long COVID. Currently, limited information exists about long-term oral health manifestations in COVID-19 patients with limited healthcare access. MethodsWe conducted a sequential, cross-sectional study (December 2020-March 2024) to assess how racial/ethnic differences (Black/Hispanic vs White/Asian) and health disparities affect oral and non-oral long COVID symptoms and their relationship with COVID-19 vaccination. We retrospectively reviewed patients oral health record from University of Illinois Chicago dental clinics before vaccination (December 2020; N=1150; Covid+/- N=575/group) and after vaccination (December 2021; N=592; Covid+/- N=292/group). Participants were recruited in two separate prospective groups of COVID-19 positive subjects (February-April 2021; pre-vaccination: N=158; January-March 2024; post-vaccination: N=171), we examined clinical indicators of oral (periodontal and salivary glands) and non-oral (neurologic) sequalae 3-6 months after initial exposure. We measured viral S protein by flow cytometry and quantified inflammatory markers, viral entry receptors, and oral viral load to correlate molecular, and cellular changes in COVID-19 positive subjects before and after vaccination. ResultsOur results identified racial disparity indicating oral associated post-acute sequelae (PASC) primarily manifested as periodontal (gum) disease (COVID-19 positive: 73.1{+/-}18.9% vs COVID-19 negative: 33.1{+/-}14.3%) and correlated with higher rates of dry mouth (57.5%), taste disturbance (47%), and smell loss (20%). Vaccination reduced oral PASC in COVID-19 positive subjects; however, periodontal disease indicators persisted compared to the COVID-19 negative group. Notably, 3-6 months post-infection, while SARS-CoV-2 Spike (S) transcript was rarely detected in saliva ([~]6%), its protein was commonly detected ([~]70%) in the COVID-19 positive subjects indicating incomplete viral clearance. This correlates with significantly higher salivary expression of viral entry receptors (ACE2, and TRMPSS2), and inflammatory mediators (IL-6, IL-8 and MMP-8), in COVID-19 positive subjects. This finding was further supported by higher prevalence of other oral viruses including Epstein-Barr Virus (70.5%), Herpes Simplex Virus (8.1%), and Human Papillomavirus (17.5%) in COVID-19 positive subjects. InterpretationCOVID-19 history significantly correlates with severe oral health complications in predominantly Black communities, while vaccination reduced but did not eliminate these issues. The oral cavity serves as a long-term viral reservoir, and periodontal inflammation with increased oral viral presence in COVID-positive patients may increase susceptibility to oral and non-oral viral diseases and identify risk for long COVID.

microbiology↗

bioRxiv2024

Myeloid-derived Suppressor Cells Mitigate Inflammation in Periodontal Disease

Myeloid derived suppressor cells (MDSCs) are a heterogeneous population of immature, immune suppressive myeloid cells. However, their role in periodontal disease (PD), a microbially induced inflammatory oral disease, remains understudied. Here we show that gingiva (gums) from PD patients exhibit significantly higher levels of MDSC markers including Granulocytic (G)-MDSC and Monocytic (M)-MDSC subsets as well as CD4+ T cells and CD19+ B cells. Gingival MDSC subsets exhibit potent immunoregulatory activity as marked by attenuated autologous CD4+ T cells proliferation and IFN{gamma} production. In a murine model of ligature-induced periodontitis (LIP), we noticed time-dependent gingival MDSC infiltration, which correlates with CD4+ T cell and CD19+ B cell infiltration. To test whether MDSC confer immunoregulatory function in vivo, we adoptively transferred G-MDSCs and M-MDSCs in mice. Interestingly, we observed significant reduction in inflammatory marker expression (IL6, TNF-, and IL-1{beta}), infiltration of CD4+ T cells, and concomitant increase in MDSC-derived immune suppressive molecules, ARG1 and IL-10, and CD4+CD25+FoxP3+ Tregs compared to mock. Conversely, depletion of MDSC using anti-Gr1 antibody resulted in marked induction of periodontal inflammation, reduced Treg population, and significantly higher alveolar bone loss. These findings, for the first time, suggest an anti-inflammatory and osteoprotective function of MDSCs in PD and offer a promising target to treat unresolved periodontal inflammation.

immunology↗

bioRxiv2023

Dynamic Changes in Macrophage Polarization during the Resolution Phase of Periodontal Disease

Periodontal inflammation is largely governed by infiltration of myeloid cells, in particular macrophages. Polarization of M{varphi} within the gingival tissues is a well-controlled axis and has considerable consequences for how M{varphi} participate in inflammatory and resolution (tissue repair) phases. We hypothesize that periodontal therapy may instigate a pro-resolution environment favoring M2 M{varphi} polarization and contribute towards resolution of inflammation post-therapy. We aimed to evaluate the markers of macrophage polarization before and after periodontal therapy. Gingival biopsies were excised from human subjects with generalized severe periodontitis, undergoing routine non-surgical therapy. A second set of biopsies were excised after 4-6 weeks to assess the impact of therapeutic resolution at the molecular level. As controls, gingival biopsies were excised from periodontally healthy subjects, undergoing crown lengthening. Total RNA was isolated from gingival biopsies to evaluate pro- and anti-inflammatory markers associated with macrophage polarization by RT-qPCR. Mean periodontal probing depths, CAL and BOP reduced significantly after therapy and corroborated with the reduced levels of periopathic bacterial transcripts after therapy. Compared to heathy and treated biopsies, higher load of Aa and Pg transcripts were observed in disease. Lower expression of M1M{varphi} markers (TNF-, STAT1) were observed after therapy as compared to diseased samples. Conversely, M2M{varphi} markers (STAT6, IL-10) were highly expressed in post-therapy as opposed to pre-therapy, which correlated with clinical improvement. These findings corroborated with murine ligature-induced periodontitis and resolution model, comparing the respective murine M{varphi} polarization markers (M1 M{varphi}: cox2, iNOS2 and M2 M{varphi}: tgm2 and arg1). Our findings suggest that imbalance in M1 and M2 polarized macrophages by assessment of their markers can provide relevant clinical information on the successful response of periodontal therapy and can be used to target non-responders with exaggerated immune responses.

immunology↗