Toll like receptors in diseases of the lung

Abstract

The lung is in continuous contact with a diverse array of infectious agents, foreign antigens, and host-derived danger signals. To sample this expansive internal and external milieu, both resident myeloid and stromal/structure cells of the lung express a full complement of toll like receptors (TLRs) which recognize pathogen-associated molecular patterns (PAMPs) and endogenous danger-associated molecular patterns (DAMPs). TLRs play a vital role in immune host defense against bacterial, mycobacterial, fungal, and viral pathogens of the lung. Additionally, TLRs contribute to disease pathogenesis in non-infectious pulmonary disorders, including airways disease, acute lung injury, and interstitial lung disease. In this review, TLR biology in the context of experimental infectious and non-infectious lung disease is discussed, and correlates to human lung disease, including therapeutic implications of these findings, are defined.

The interaction of influenza H5N1 viral hemagglutinin with sialic acid receptors leads to the activation of human γδ T cells

“…45 Myeloid dendritic cells and alveolar macrophages in the lung express high levels of TLRs, such as TLR2, TLR3 and TLR4, which are important for the recognition of influenza viruses. 43,44 However, cell surface expression of TLRs in human peripheral blood cd T cells was nearly undetectable by flow cytometry, indicating that TLRs may not be involved in the response of cd T cells to influenza virus and that the PRR-mediated signaling pathway may not play an essential role in the activation of human cd T cells in influenza H5N1 virus infection. NK cells, which represent another important cell population in the innate immune response to viral infections, are activated by influenza virus HA proteins through interaction with the NKp46 receptor.…”

“…[43][44][45] Therefore, we determined whether rHA-induced cd T-cell activation is mediated by these receptors. We found no surface expression of TLR2, TLR3 or TLR4 on cd T cells (Figure 6a).…”

Epigenetic Regulation of Tolerance to Toll-Like Receptor Ligands in Alveolar Epithelial Cells

“…Primary human type II AECs express both mRNA and protein for functional TLR2 and TLR4 (45). Since that discovery, several studies have explored the role of TLRs on structural cells and how they might function to protect the lung against infectious and noninfectious stimuli (46). For example, exposure of lung epithelial cells to environmental particulates resulted in down-regulation of TLR4, but TLR2 expression, which was associated with reduced responsiveness to LPS in both lung macrophages and epithelial cells (47).…”

Impact of air pollution on lung inflammation and the role of Toll-like receptors

“…6,81,84,85 As shown in Table 1, TLRs are found on the surface of a multitude of cells (TLR1-6, 10) and intracellularly within endosomes (TLR3, 7/8, 9). 85 TLR structure, detailed in Figure 2, is characterized by an amino-terminal extracellular leucine-rich repeat domain and an intracellular Toll/IL-1 receptor (TIR) responsible for ligand binding and signal transduction, respectively. 80 The TLR family of receptors are type 1 integral membrane glycoproteins with structural homology in the cytoplasmic region to the larger superfamily of IL-1 receptors.…”

“…85 Research in this field has novel implications for reducing the overall health burden posed by exposure to air pollution and should be actively pursued.…”