TLR4 signalling in pulmonary stromal cells is critical for inflammation and immunity in the airways

Frederic Perros,Bart N Lambrecht,Hamida Hammad

doi:10.1186/1465-9921-12-125

Frederic Perros, Bart N Lambrecht + Show 1 more

Open Access

https://doi.org/10.1186/1465-9921-12-125

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Journal: Respiratory research	Publication Date: Dec 1, 2011
Citations: 129	License type: cc-by

Affiliation: Ghent University Hospital

Abstract

Inflammation of the airways, which is often associated with life-threatening infection by Gram-negative bacteria or presence of endotoxin in the bioaerosol, is still a major cause of severe airway diseases. Moreover, inhaled endotoxin may play an important role in the development and progression of airway inflammation in asthma. Pathologic changes induced by endotoxin inhalation include bronchospasm, airflow obstruction, recruitment of inflammatory cells, injury of the alveolar epithelium, and disruption of pulmonary capillary integrity leading to protein rich fluid leak in the alveolar space. Mammalian Toll-like receptors (TLRs) are important signalling receptors in innate host defense. Among these receptors, TLR4 plays a critical role in the response to endotoxin.Lungs are a complex compartmentalized organ with separate barriers, namely the alveolar-capillary barrier, the microvascular endothelium, and the alveolar epithelium. An emerging theme in the field of lung immunology is that structural cells (SCs) of the airways such as epithelial cells (ECs), endothelial cells, fibroblasts and other stromal cells produce activating cytokines that determine the quantity and quality of the lung immune response. This review focuses on the role of TLR4 in the innate and adaptive immune functions of the pulmonary SCs.

Highlights

Inflammation of the airways, which is often associated with life-threatening infection by Gram-negative bacteria or presence of endotoxin in the bioaerosol, is still a major cause of severe airway diseases
Endotoxin sensing by pulmonary stromal cells As depicted above, LPS signalling through TLR4 in pulmonary epithelial cells (ECs) involves at least the signal-transducing molecules MyD88, IL-1R-associated kinase (IRAK), and TRAF6 and activation of the transcription factor NF-B [23]
The results of Skerrett et al [41] and those of Poynter et al [42] suggest that NF-B activation in respiratory ECs contributes to the lung inflammatory response to inhaled LPS through the induction of proinflammatory cytokines, which in turn act to upregulate the expression of adhesion molecules on the vascular endothelium

Summary

Introduction

Inflammation of the airways, which is often associated with life-threatening infection by Gram-negative bacteria or presence of endotoxin in the bioaerosol, is still a major cause of severe airway diseases. Guillot et al [23] showed that ECs response to LPS involves at least the signal-transducing molecules MyD88, IRAK, and TRAF6 and activation of the transcription factor NF-B.

Results

Conclusion