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Review
. 2025 Apr 18;26(1):34.
doi: 10.1186/s12865-025-00713-8.

Natural and induced immune responses in oral cavity and saliva

Affiliations
Review

Natural and induced immune responses in oral cavity and saliva

Michele Matsuoka et al. BMC Immunol. .

Abstract

This review comprehensively explores the intricate immune responses within the oral cavity, emphasizing the pivotal role of saliva in maintaining both oral and systemic health. Saliva, a complex biofluid, functions as a dynamic barrier against pathogens, housing diverse cellular components including epithelial cells, neutrophils, monocytes, dendritic cells, and lymphocytes, which collectively contribute to robust innate and adaptive immune responses. It acts as a physical and immunological barrier, providing the first line of defense against pathogens. The multifaceted protective mechanisms of salivary proteins, cytokines, and immunoglobulins, particularly secretory IgA (SIgA), are elucidated. We explore the natural and induced immune responses in saliva, focusing on its cellular and molecular composition. In addition to saliva, we highlight the significance of a serum-like fluid, the gingival crevicular fluid (GCF), in periodontal health and disease, and its potential as a diagnostic tool. Additionally, the review delves into the impact of diseases such as periodontitis, oral cancer, type 2 diabetes, and lupus on salivary immune responses, highlighting the potential of saliva as a non-invasive diagnostic tool for both oral and systemic conditions. We describe how oral tissue and the biofluid responds to diseases, including considerations to periodontal tissue health and in disease periodontitis. By examining the interplay between oral and systemic health through the oral-systemic axis, this review underscores the significance of salivary immune mechanisms in overall well-being and disease pathogenesis, emphasizing the importance of salivary mechanisms across the body.

Keywords: Barriers; Host response; Host-microbial interactions; Immunity; Microbiome; Saliva.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: No subject’s evaluation participated in this review manuscript. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Salivary and Mucosal Barriers and Responses. Free-floating cells and proteins found within saliva will prevent microbes from disrupting the mucosal epithelial layer. At the moment of infection or cell damage within the epithelial layer, the targeted cell will send signals out to dendritic cells that will then migrate to the lymph nodes and mature in the form of APCs. These APC’s will then activate subsets of T cells (CD8+ or CD4+) responsible for the activation of the humoral or cellular response which can either alleviate infections or exacerbate inflammation

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