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Barrier immunity; Epithelial cells; Innate immunity; Pattern recognition receptors; Antimicrobial peptides; Mucosal surfaces; Immune dysregulation; Inflammatory diseases

Introduction

The human body is constantly exposed to a diverse array of pathogens, environmental insults, and toxins, yet it maintains a remarkable ability to protect itself from infection and disease. This protection is largely mediated by barrier immunity, a complex system that integrates physical, chemical, and immune responses [1]. The epithelial cells that line mucosal surfaces—such as the skin, respiratory tract, and gastrointestinal tract—form the first line of defense, providing both a physical barrier and an active immune response. Barrier immunity is not a passive defense system. It actively senses microbial threats through pattern recognition receptors (PRRs), such as toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), and RIG-I-like receptors (RLRs), which recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) [2]. Upon pathogen detection, epithelial cells initiate a cascade of immune responses, including the production of antimicrobial peptides, cytokines, and chemokines that recruit and activate other immune cells, including neutrophils, macrophages, and dendritic cells. Although the primary role of barrier immunity is to prevent pathogen entry, its function is much broader, maintaining immune homeostasis and preventing excessive inflammation. Dysregulation of barrier immunity can contribute to the development of a variety of inflammatory and autoimmune diseases [3]. This review will explore the mechanisms of barrier immunity, with a focus on the contributions of epithelial cells to host defense, the interaction with innate immune cells, and the consequences of barrier dysfunction.

Results

Role of epithelial cells in barrier immunity

Epithelial cells serve as both a physical barrier and an active immune sensor. Structurally, they form tight junctions that prevent the entry of pathogens and toxins. These cells also produce antimicrobial peptides (AMPs), such as defensins, cathelicidins, and lysozymes, which directly target and neutralize microorganisms at mucosal surfaces. Upon encountering pathogens, epithelial cells activate intracellular signaling pathways involving PRRs like TLRs, which recognize conserved molecular patterns associated with pathogens [4]. The engagement of TLRs and other PRRs triggers the release of pro-inflammatory cytokines (e.g., TNF-α, IL-6) and chemokines (e.g., IL-8), which recruit immune cells to the site of infection. Epithelial cells also play a critical role in orchestrating adaptive immunity by interacting with dendritic cells. Through the release of cytokines, they help drive the differentiation of naïve T cells into effector T cells, further amplifying the immune response.

Interaction with immune cells

Neutrophils, macrophages, and dendritic cells are key components of the innate immune system that are recruited to sites of infection through signals from epithelial cells [5]. Neutrophils, which are the first responders to infection, release reactive oxygen species (ROS) and proteolytic enzymes to eliminate pathogens. Macrophages are involved in pathogen clearance through phagocytosis and antigen presentation, while dendritic cells bridge the innate and adaptive immune responses by activating T cells. Moreover, recent research has highlighted the role of the microbiota in modulating barrier immunity [6]. The gut microbiome, for example, influences epithelial cell function and immune cell differentiation, with alterations in microbial composition contributing to the pathogenesis of inflammatory diseases like inflammatory bowel disease (IBD).

Discussion

The concept of barrier immunity extends beyond its protective function against pathogens. It plays a central role in maintaining immune tolerance and homeostasis. This is particularly evident in the gut, where a delicate balance between immune activation and suppression is critical to preventing inflammatory diseases. Dysregulation of barrier immunity, especially in the form of epithelial barrier breakdown or aberrant immune responses, can lead to chronic inflammatory conditions such as Crohn's disease, asthma, and allergic skin disorders [7]. One of the major challenges in understanding barrier immunity is its complexity and the fact that different tissues exhibit distinct mechanisms of immune surveillance and response. The skin, for instance, relies on a different set of antimicrobial peptides and immune cell interactions than the gastrointestinal tract or lungs. Additionally, the interactions between epithelial cells and the microbiota complicate the immune responses in these tissues, as both beneficial and harmful microorganisms can influence immune function [8]. Recent advances in immunology have highlighted the dynamic interplay between epithelial cells, immune cells, and the microbiome. The gut-associated lymphoid tissue (GALT) is an excellent model for studying these interactions, as it is exposed to a constant stream of antigens and pathogens while maintaining tolerance to commensal microbes. Dysbiosis—an imbalance in the microbiota—can compromise the integrity of the epithelial barrier and contribute to diseases such as IBD and allergies. Furthermore, while the epithelial layer plays an essential role in initiating immune responses, it is also critical in maintaining a state of immune tolerance. Overactivation of the immune system due to persistent inflammation can lead to autoimmune diseases. Thus, a balance between immune activation and suppression is crucial for proper barrier function.

Conclusion

Barrier immunity is a multifaceted defense system that involves epithelial cells, innate immune receptors, antimicrobial peptides, and immune cell interactions to protect the body from infections while maintaining homeostasis. Epithelial cells, through their direct interaction with pathogens and the immune system, serve as a critical component of this defense. Dysregulation of barrier immunity can lead to chronic inflammatory diseases, autoimmune disorders, and increased susceptibility to infections. As our understanding of barrier immunity grows, it opens new avenues for therapeutic interventions aimed at restoring barrier function and preventing immune-related diseases. Future research should focus on elucidating the specific molecular mechanisms that govern the interactions between epithelial cells, immune cells, and the microbiota. Additionally, novel therapies that target epithelial cell function or modulate immune responses could offer new treatments for diseases associated with barrier dysfunction.

1. Ampomah IG, Malau BS, Aduli AE, Emeto TI (2020) Medicina 56: 271.

, ,

2. Irwin MR, Opp MR (2017) Neuropsychopharmacology 42: 129-155.

, ,

3. Gamache R, Kharrazi H, Weiner JP (2018) Year Book of Medical Informatics 27: 199-206.

, ,

4. Jandoo T (2020)

,

5. Ahola-Launonen J (2016) Cambridge Quarterly of Healthcare Ethics 25: 448-465.

,

6. Land T (2019) Frontiers of Health Services Management 36: 1-2.

, ,

7. Driver TH, Wachter RM (2012) Journal of Hospital Medicine 7: 60-65.

, ,

8. Sinclair JR (2019 Revue Scientifique et Technique 38: 145-154.

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