Innate Immunity in the Respiratory Epithelium

Abstract

The airway epithelium represents the first point of contact for inhaled foreign organisms. The protective arsenal of the airway epithelium is provided in the form of physical barriers and a vast array of receptors and antimicrobial compounds that constitute the innate immune system. Many of the known innate immune receptors, including the Toll-like receptors and nucleotide oligomerization domain-like receptors, are expressed by the airway epithelium, which leads to the production of proinflammatory cytokines and chemokines that affect microorganisms directly and recruit immune cells, such as neutrophils and T cells, to the site of infection. The airway epithelium also produces a number of resident antimicrobial proteins, such as lysozyme, lactoferrin, and mucins, as well as a swathe of cationic proteins. Dysregulation of the airway epithelial innate immune system is associated with a number of medical conditions that can result in compromised immunity and chronic inflammation of the lung. This review focuses on the innate immune capabilities of the airway epithelium and its role in protecting the lung from infection as well as the outcomes when its function is compromised.

FOXO Transcription Factors Regulate Innate Immune Mechanisms in Respiratory Epithelial Cells

“…Considering these points, we assumed that FOXO is involved in an endosomal pathway that requires uptake and degradation of the pathogen. TLR3 is one of the pattern recognition receptors localized in the endosomal compartment (12,38) and can easily be targeted, unlike TLR4, which is additionally expressed on the cell membrane, thereby triggering distinct signaling mechanisms that are difficult to discriminate (39). Therefore, we decided to focus on TLR3 signaling.…”

“…As in immune cells, the cellular response of epithelial cells activated by TLRs can be MyD88-dependent or -independent (12). In respiratory epithelial cells, activation of cell surface-expressed TLR2, TLR4, and TLR5 by their specific ligands (lipoproteins, LPS, and flagellin) leads to the expression of inflammatory mediators and antimicrobial peptides (AMPs) mediated by NF-kB and MAPK signaling cascades, whereas activation of endosomal TLR3 and TLR4 results in the expression of type 1 IFNs in a TRIF-dependent manner (12). TLR3 is commonly known to be important during viral infection recognizing dsRNA.…”

The regulation of host defences to infection by the microbiota

“…These innate effectors are supplemented by lung dendritic cells that transport antigen to draining lymph nodes for the development of adaptive responses, which are crucial for the clearance of many respiratory pathogens 53. Central to the coordination of all these airway defences is initial microbial recognition by pattern recognition receptors (PRRs) leading to the production of a variety of signalling molecules 52, 55. These include type I interferons during viral infection,56 and cytokines such as granulocyte–macrophage colony‐stimulating factor, interleukin‐22 (IL‐22), IL‐23 and IL‐17, which orchestrate both innate and adaptive antibacterial immunity 51, 52, 53, 57.…”

“…Central to the coordination of all these airway defences is initial microbial recognition by pattern recognition receptors (PRRs) leading to the production of a variety of signalling molecules 52, 55. These include type I interferons during viral infection,56 and cytokines such as granulocyte–macrophage colony‐stimulating factor, interleukin‐22 (IL‐22), IL‐23 and IL‐17, which orchestrate both innate and adaptive antibacterial immunity 51, 52, 53, 57. Innate defences against infection have generally been considered ‘hard‐wired’ – a specific infection will elicit a defined, stereotypical immune response 58, 59, 60.…”

Variation in Genome-wide NF-kappaB RELA Binding Sites upon Microbial Stimuli and Identification of a Virus Response Profile

“…Particularly following TLR3 stimulation, which showed a distinct NF-kB response that was not well described previously. This work is relevant in regards to the innate immune response to pathogen infection, particularly airborne microbes in the nasopharynx, where the role of epithelial cells in recognizing pathogens is crucial 35 .…”