Biology subjects

Greenwell-Wild, T.

Publications and source records attributed to Greenwell-Wild, T..

4 recordsLinked to original sources

bioRxiv2026

IgG sequencing maps systemic antibody binding to oral commensals and pathobionts in health and periodontitis

The oral cavity harbors one of the body's most diverse microbial communities, which continuously seeds the bloodstream and gastrointestinal tract, particularly in periodontitis, a disease in which both barrier permeability and microbial burden increase. Despite this constant systemic exposure, overt bacteremia from oral organisms is rare, suggesting an active surveillance system that contains this reservoir. Here, we apply IgG-sequencing to comprehensively map mucosal and systemic antibody recognition of the oral microbiome across paired oral fluid and serum from healthy individuals and patients with periodontitis. We find that IgG-binding is only weakly predicted by microbial abundance, suggesting taxon-specific and largely conserved IgG-binding of commensals, many of them streptococci which dominate antibody recognition irrespective of disease state. Periodontitis broadens the repertoire of IgG-bound taxa to include particular disease-associated pathobionts while preserving robust targeting of health-associated symbionts. Comparison of salivary and serum antibody profiles further uncovers a subset of commensal streptococci, including species implicated in infective endocarditis, that acquire disproportionate systemic IgG binding in periodontitis. Together, these findings establish a taxon-level atlas of humoral immunosurveillance at a major mucosal-microbial interface and reveal how periodontal disease reshapes systemic antibody recognition of both pathobionts and commensals.

immunology↗

bioRxiv2026

Mucosal Inflammation Shapes Human Neutrophil States in Tissue and Circulation

The oral mucosa is a prototypical human barrier reliant on neutrophils for homeostasis, as both neutrophil deficiency and excessive activation are linked to immunopathology. Yet, whether neutrophils acquire tissue-specific states in health or disease remains unclear. We incorporated single-cell RNA sequencing, spectral flow cytometry, and spatial proteomics across tooth-associated oral mucosa (gingiva) and interconnected compartments of blood and oral cavity to define neutrophil tissue specification in healthy individuals and patients with periodontitis, a neutrophil-dominated inflammatory disease. In health, mucosal neutrophils adopt discrete immunoregulatory states despite constant microbial exposure and mechanical injury. Periodontitis disrupts these programs through infiltration of blood-like neutrophil subsets, increased transcriptional noise, and heightened effector activation. Strikingly, oral inflammation systemically imprints on circulating neutrophils, marked by the expansion of a Rho-GTPase regulatory program that is shared across diverse human inflammatory conditions. Together, these findings establish a framework for understanding how localized tissue inflammation affects both neutrophil plasticity at barrier surfaces and conditioning of systemic neutrophil states with broad implications for inflammatory disease pathogenesis.

immunology↗

bioRxiv2021

Single-cell atlas of human oral mucosa reveals a stromal-neutrophil axis regulating tissue immunity in health and inflammatory disease

The oral mucosa remains an understudied barrier tissue rich in exposure to antigens, commensals and pathogens. Moreover, it is the tissue where one of the most prevalent human microbe-triggered inflammatory diseases, periodontitis, occurs. To understand this complex environment at the cellular level, we assemble herein a human single-cell transcriptome atlas of oral mucosal tissues in health and periodontitis. Our work reveals transcriptional diversity of stromal and immune cell populations, predicts intercellular communication and uncovers an altered immune responsiveness of stromal cells participating in tissue homeostasis and disease at the gingival mucosa. In health, we define unique populations of CXCL1,2,8-expressing epithelial cells and fibroblasts mediating immune homeostasis primarily through the recruitment of neutrophils. In disease, we further observe stromal, particularly fibroblast hyper-responsiveness linked to recruitment of leukocytes and neutrophil populations. Ultimately, a stromal-neutrophil axis emerges as a key regulator of mucosal immunity. Pursuant to these findings, most Mendelian forms of periodontitis were shown to be linked to genetic mutations in neutrophil and select fibroblast-expressed genes. Moreover, we document previously unappreciated expression of known pattern- and damage-recognition receptors on stromal cell populations in the setting of periodontitis, suggesting avenues for triggering stromal responses. This comprehensive atlas offers an important reference for in-depth understanding of oral mucosal homeostasis and inflammation and reveals unique stromal-immune interactions implicated in tissue immunity.

systems biology↗

bioRxiv2021

Fibrin is a critical regulator of neutrophil effector function at mucosal barrier sites

Tissue-specific cues are critical for homeostasis at mucosal barriers. Here, we document that the clotting factor fibrin is a critical regulator of neutrophil function at mucosal barriers. We demonstrate that fibrin engages neutrophils through the M{beta}2 integrin receptor and activates effector functions, including the production of reactive oxygen species and NET formation. These immune-protective neutrophil functions become tissue damaging in the context of impaired plasmin-mediated fibrinolysis. Indeed, the accumulation of fibrin due to Mendelian genetic defects in plasmin leads to severe oral mucosal immunopathology in mice and humans. Concordantly, genetic polymorphisms in the human PLG gene, encoding plasminogen, are associated with common forms of the oral mucosal disease periodontitis. Our work uncovers fibrin as a critical regulator of neutrophil effector function within the mucosal tissue microenvironment and suggests fibrin-neutrophil engagement as a pathogenic instigator and therapeutic target in common mucosal disease.

immunology↗