Distinct immune landscapes between murine and human periodontitis

Periodontitis (PD) affects over 1 billion people globally, underscoring the need for valid animal models. This study aimed to (1) systematically compare single-cell immune landscapes between human PD and murine ligature models, and (2) evaluate whether <i>Porphyromonas gingivalis</i> (Pg) supplementation improves model translatability. Using single-cell RNA sequencing (scRNA-seq) of murine gingival tissues from ligature, ligature+Pg, and control groups, integrated with human data, distinct immune profiles between murine and human PD was identified: (1) Murine models showed significantly lower B/plasma cell Δ(PD-Ctrl) proportions than human (murine 0.10% vs. human 22.39%, <i>p</i> < 0.001) and attenuated activation states; (2) Conversely, the change in macrophages Δ(PD-Ctrl) is significantly greater in mice (murine 28.53% vs. human -6.603%, <i>p</i> < 0.0001) and exhibited hyperactivation; (3) Co-administration of Pg did not reduce the immunological distinctions between mice and humans. (<i>p</i> > 0.05). These findings reveal immunological disparities in murine ligature models from human PD, suggesting to approach with caution when using these models for studying immune interactions in PD.