Allergic Airway Inflammation Inhibits Pulmonary Antibacterial Host Defense

Abstract

The innate immune system of the lung is a multicomponent host defense system and in addition has an instructing role in regulating the quality and quantity of the adaptive immune response. When the interaction between innate and adaptive immunity is disturbed, pathological conditions such as asthma can develop. It was the aim of the study to investigate the effect of the allergic inflammation of the lung on the innate host defense during bacterial infection. Human bronchial epithelial cells were preincubated with Th2 cytokines and infected with Pseudomonas aeruginosa. The effect of the Th2 cytokines on the mRNA levels of antimicrobial peptides and the antimicrobial activity of HBEC was determined. To investigate the influence of an allergic inflammation on pulmonary host defense in vivo, mice sensitized and challenged with OVA were infected with P. aeruginosa, and the number of viable bacteria in the lungs was determined together with markers of inflammation like cytokines and antimicrobial peptides. Exposure of airway epithelial cells to Th2 cytokines resulted in a significantly decreased antimicrobial activity of the cells and in suppressed mRNA levels of the antimicrobial peptide human β-defensin 2. Furthermore, mice with allergic airway inflammation had significantly more viable bacteria in their lungs after infection. This was consistent with reduced levels of proinflammatory cytokines and of the antimicrobial peptide cathelin-related antimicrobial peptide. These results show that an allergic airway inflammation suppresses the innate antimicrobial host defense. The adaptive immune system modulates the functions of the pulmonary innate immune system.

International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma

“…Toll-like receptor signalling may also be impaired, leading to inadequate Type I and III interferon (IFN) responses which decrease viral clearance [86]. In addition, the antimicrobial activity of airway epithelial cells and their production of b-defensins are reduced when these cells are exposed to Th2 cytokines, while allergic inflammation leads to a reduction in cathelicidin antimicrobial peptide [87,88]. In contrast, other elements of innate immunity may be enhanced, including increased expression of thymic stromal lymphopoietin, IL-25 and IL-33 in airway cells from patients with severe asthma [70,89,90].…”

FOXO Transcription Factors Regulate Innate Immune Mechanisms in Respiratory Epithelial Cells

“…We used a murine model of pneumonia (34) to examine whether bacterial infection of the respiratory tract induces the activation of FOXO transcription factors in epithelial cells. Lungs of mice were infected with either P. aeruginosa PAO1 or NTHi.…”

Beyond inflammation: airway epithelial cells are at the interface of innate and adaptive immunity

“…Likewise, the vast majority of patients with severe polypoid chronic rhinosinusitis have S. aureus colonization in their upper airways while only a fourth of normal subjects carry nasal S. aureus [15]. Experimentally, recent findings show that exposure of airway epithelial cells to the Th2 cytokines IL-4 and IL-13 resulted in a significant decrease in antimicrobial activity of the cells and suppressed mRNA levels of the antimicrobial peptide human β-defensin 2 but not human β-defensin 1 or LL-37 [16]. Furthermore, mice with allergic airway inflammation had significantly more viable bacteria in their lungs after infection.…”