Cytokines, chemokines, and immune cells involved in oral immunity towards the dental cariogenic bacterium Streptococcus mutans: Therapeutic interventions and vaccination

Untreated dental caries, or tooth decay, is the most frequent health-related affliction, mainly due to insufficient service in low- and middle-income countries. The inflammatory niche in the presence of Streptococcus mutans and its biofilm in the oral cavity can lead to immune-mediated tissue injury, enamel demineralization, cavitation, pulp infection, dental loss, and extraoral disorders such as endocarditis. Recruiting immune responses to fight pathogens is a novel therapeutic strategy that prevents antimicrobial resistance and regulates the immune microenvironment. Within this manuscript, the host's determinative innate and adaptive immune functions in the progression or regression of dental caries are introduced. Primarily, the correlation of S. mutans and its virulence factors, such as antigenI/II, quorum-sensing peptides, collagen-binding proteins, glucosyltransferases, and lipoteichoic acid on oral immunopathology has been classified. The role of phagocytosis, NETosis, and pyroptosis on pathogen clearance and the effect of virulence factors on the immune markers in the secretome of dendritic cells, dental pulp stem cells, and odontoblasts are described. The placement of natural products, antimicrobial peptides, probiotics, stem cells, nanoparticles, and irradiation involved in the immunotherapy of dental caries is investigated. The nasopharynx-associated lymphoid tissue in mucosal administration of the anti-caries vaccine is critical. Therefore, the effects of immunodominant antigens, delivery vectors, promoters, endogenous inhibitory microRNAs, the prime-boost vaccination strategy, and co-immunization of genetic vaccines with cytokines and chemokines as adjuvants on immunocyte activation, salivary IgA, and specific serum IgG in caries prevention are determined. Conclusively, successful therapeutic interventions that recruit oral immunity to eradicate S. mutans affected ERK/MAPK, NF-κB, and inflammasome signaling pathways in favor of Th1 response suppression. The most effective caries preventive vaccines produced a combination of Th1, Th2, and Th17 responses. Finally, multivalent vaccines inhibiting the activation of suppressor of cytokine signaling (SOCS) genes are proposed for the successful development of anti-caries vaccine.