Unveiling the immune dynamics of Neisseria persistent oral colonization: a roadmap for innovative vaccine strategies

Abstract

Abstract Commensals shape host physiology and immunity. Neisseria gonorrhoeae (NG), a human pathogen, causes asymptomatic colonization and animal studies on NG for vaccine-design have been unsuccessful. N. musculi (NM), a mouse commensal, shares host-interaction genes with NG and is a surrogate to study NG colonization. Eight A/J mice were orally inoculated with NM; uninoculated mice served as controls (n=8). Four from each group were euthanized at day 5 and the rest at day 33. Immune signatures and palate transcriptome were compared between inoculated and control mice using Wilcoxon rank-sum test. Transcriptomics revealed enriched mucosal immunity and inflammation in colonized tissue. Day 5 data suggested reduced colonization resistance (reduced monocytes), while data at day 33 showed enriched adaptive (memory B cells) and immunoregulatory cells (Tregs) in colonized tissue. At day 5 of colonization, systemic immune response was pro-inflammatory. Splenic NK cells showed higher IL22, suggesting reinforcement of mucosal immunity during colonization. Systemic immune response displayed reduced enrichment of immune signatures at day 33 of colonization suggesting homeostasis. Positive correlations between NM palate colony counts and enriched immune subsets suggest impact of mucosal colonization on immunophenotypes (p<0.05 for all). This data is crucial for defining transcriptional and immunological endpoints of NM mucosal colonization, aiding in developing vaccine candidates against NG.