CONTRIBUTION OF TOLL-LIKE RECEPTORS TO THE IMMUNE RESPONSE IN UPPER RESPIRATORY TRACT INFECTIONS

Аннотация

Upper respiratory tract infections (URTIs) are among the most common infectious diseases worldwide, caused primarily by viruses and, less frequently, by bacteria. Toll-like receptors (TLRs), as key components of the innate immune system, play a central role in recognizing pathogen-associated molecular patterns (PAMPs) and initiating immune responses in the respiratory epithelium. This article reviews the expression and function of TLRs in the upper respiratory tract, their involvement in pathogen detection, and the consequences of dysregulated TLR signaling. Understanding TLR-mediated mechanisms in URTIs may aid in developing novel immunomodulatory therapies. 1.Introduction The upper respiratory tract serves as the primary entry point for a variety of airborne pathogens, including viruses such as rhinoviruses, influenza viruses, and coronaviruses, as well as bacteria like Streptococcus pneumoniae. Toll-like receptors (TLRs) are essential pattern recognition receptors (PRRs) that detect microbial components and trigger innate immune responses (Kawai & Akira, 2010). In the respiratory mucosa, epithelial cells and immune cells express TLRs that contribute to early pathogen recognition and shaping of adaptive immunity (Bals & Hiemstra, 2004). 2.ExpressionandLocalization ofTLRsin theUpper Respiratory Tract Different TLRs are differentially expressed in various cell types of the upper airway, including nasal epithelial cells, macrophages, and dendritic cells. TLR3, TLR7, and TLR8 are primarily located in endosomes and recognize viral RNA, while TLR2 and TLR4, expressed on the cell surface, detect bacterial lipoproteins and lipopolysaccharides, respectively (Kaisho & Akira, 2006). For instance, nasal epithelial cells express high levels of TLR3 and TLR7, which are essential for recognizing influenzaand rhinoviral infections (Hajjar et al., 2002). The upper respiratory tract (URT), which includes the nasal passages, nasopharynx, and oropharynx, is the first line of defense against inhaled pathogens. Toll-like receptors (TLRs) are expressed by various cell types in the URT, including epithelial cells, dendritic cells (DCs), macrophages, and endothelial cells. Their expression patterns and cellular localization are essential for initiatingimmuneresponses against bothbacterial and viral pathogens. TLR Expression inNasalandRespiratory Epithelium The respiratory epithelium, which forms the mucosal barrier of the URT, expresses several TLRs, with the highest expression levels observed for TLR2, TLR3, TLR4, and TLR5. These TLRs are crucial for detecting pathogen-associated molecular patterns (PAMPs) such as lipoproteins,lipopolysaccharides, flagellin, andviral RNA.  TLR2 is highly expressed on the surface of nasal epithelial cells, particularly those in the upper respiratory tract. It recognizes components of Gram-positive bacteria (e.g., Staphylococcus aureus, Streptococcus pneumoniae) and activates inflammatory pathways (Toshchakov et al., 2002).  TLR3, located predominantly in endosomal membranes, recognizes double-stranded RNA (dsRNA) produced by many viruses, including influenza and rhinoviruses. It is https://ijmri.de/index.php/jmsi volume 4,issue4,2025 473 expressed inepithelial cells and dendritic cells ofthe URT (Alexopoulouet al., 2001).  TLR4 is expressed on both the apical and basolateral surfaces of respiratory epithelial cells, where it plays a key role in detecting lipopolysaccharides (LPS) from Gram- negative bacteria like Haemophilus influenzae (Hoshino et al., 2002). It can also recognizeviral glycoproteins, suchas theRSV fusionprotein (Kurt-Jones et al., 2000).  TLR5, present on the apical surface of airway epithelial cells, is primarily involved in recognizing flagellin, a component of bacterial flagella. This TLR is involved in detecting motilebacteria, such as Pseudomonas aeruginosa (Hayashi et al., 2001). TLR Expression inDendriticCells and Macrophages Dendritic cells (DCs) are central to the immune response in the URT and play a critical role in TLR-mediated pathogen detection. Plasmacytoid dendritic cells (pDCs), which are abundant in the nasal mucosa, express TLR7 and TLR9 and are crucial for the detection of single-stranded RNA (ssRNA) viruses like influenza and rhinovirus (Lund et al., 2004). These pDCs produce type Iinterferons (IFNs), which are essential forlimiting viral replication. Macrophages also express multiple TLRs, including TLR2, TLR4, TLR5, and TLR9. They play akey role in clearing pathogens and promotinginflammation in response to infection. These cells are involved in both direct pathogen killing and the activation of adaptive immunity via thesecretion ofcytokines such as TNF-α,IL-6, and IL-12 (Toshchakov et al., 2002). Localization ofTLRsin Upper RespiratoryTract Tissues The localization of TLRs in the URT is important for the initial detection of pathogens that are inhaled. TLRs are localized not only in epithelial cells but also in immune cells in the nasal mucosa, sinuses