Biology subjects

Cho, G. D.

Publications and source records attributed to Cho, G. D..

3 recordsLinked to original sources

bioRxiv2026

An ex vivo gut mucosal explant assay to compare HIV tissue susceptibility shows increased HIV susceptibility with methamphetamine exposure

BackgroundExisting ex vivo mucosal explant models for HIV assess viral replication but do not fully capture the ability of tissue to support productive infection and transfer to target cells, an important indicator of tissue susceptibility. Additional tools to investigate relative mucosal susceptibility to HIV are necessary to better understand risk factors, such as substance use, or to evaluate therapeutics. ResultsWe developed an ex vivo gut mucosal explant assay incorporating a CCR5/CXCR4-expressing GFP-reporter cell co-culture to quantify both viral replication and transfer. Susceptibility was quantified using a composite metric based on time to infection endpoint across viral doses. Modulators of susceptibility, including anti-CD3 stimulation, tenofovir, and methamphetamine, were evaluated. The assay reliably detected differences in tissue susceptibility under various experimental conditions. We detected enhanced susceptibility following anti-CD3 stimulation, while tenofovir pretreatment reduced susceptibility in a dose-dependent manner. Methamphetamine exposure resulted in a modest but significant increase in gut tissue susceptibility to HIV. ConclusionsThis novel ex vivo explant susceptibility assay advances HIV mucosal transmission research by measuring both viral production and transfer. It can detect subtle changes in susceptibility, providing a versatile platform for evaluating prevention therapeutics, host and microbial factors, and substance use effects.

microbiology↗

bioRxiv2025

Comparison of oral and gut microbiome highlights role of oral bacteria in systemic inflammation in HIV

BackgroundChronic HIV-1 infection is associated with increased inflammation-related comorbidities, despite effective viral suppression with antiretroviral therapy. While the role of the gut microbiome in inflammation is well-studied, the contribution of the oral microbiome remains less clear. This study investigates the relationship between the oral and gut microbiomes in driving systemic inflammation in persons with HIV. MethodsThis cross-sectional study utilized archived samples from 198 participants (99 with HIV and 99 without HIV). Oral microbiome composition was analyzed via 16S rRNA sequencing and systemic inflammatory biomarkers were measured using multiplex assays. Gut microbiome data from previous studies were integrated for comparative analyses. Bacterial inflammatory potential was assessed through in vitro co-culture and epithelial barrier permeability assays. ResultsThe oral microbiome in HIV was characterized by increased Veillonella, Capnocytophaga, and Megasphaera, and several decreased genera including Fusobacterium. Using PERMANOVA, we found that the oral microbiome was a significant driver of cytokine variation in HIV compared to the gut microbiome, and identified specific associations with oral Veillonella and Megasphaera. We found no differences in anti-Veillonella parvula serum IgG by HIV status, but IgG titers did correlate with microbial translocation markers sCD14 and LBP in HIV. In vitro studies demonstrated that Veillonella parvula increased oral epithelial barrier permeability and induced monocyte activation. ConclusionsThe oral microbiome, particularly Veillonella parvula, may contributes to systemic inflammation in HIV through mechanisms involving epithelial barrier disruption, oral translocation, and monocyte activation.

microbiology↗

bioRxiv2022

Early life tolerance depends on a subset of specialized dendritic cells and is reinforced by the skin microbiota

Early life establishment of tolerance to commensal bacteria at barrier surfaces carries enduring implications for immune health but remains poorly understood. Here we show that this process is controlled by microbial interaction with a specialized subset of antigen presenting cells. More particularly, we identify CD301b+ type 2 conventional dendritic cells (DC) as a subset in neonatal skin specifically capable of uptake, presentation and generation of regulatory T cells (Tregs) to commensal antigens. In early life, CD301b+ DC2 are enriched for programs of phagocytosis and maturation, while also expressing tolerogenic markers. In both human and murine skin, these signatures were reinforced by microbial uptake. In contrast to their adult counterparts or other early life DC subsets, neonatal CD301b+ DC2 highly expressed the retinoic acid-producing enzyme, RALDH2, deletion of which limited commensal-specific Tregs. Thus, synergistic interactions between bacteria and a specialized DC subset critically support early life tolerance at the cutaneous interface.

immunology↗