Where Asthma and Hypersensitivity Pneumonitis Meet and Differ

Abstract

Asthma is a type-I allergic airway disease characterized by Th 2 cells and IgE. Episodes of bronchial inflammation, eosinophilic in nature and promoting bronchoconstriction, may become chronic and lead to persistent respiratory symptoms and irreversible structural airway changes. Representative mostly of mild to moderate asthma, this clinical definition fails to account for the atypical and often more severe phenotype found in a considerable proportion of asthmatics who have increased neutrophil cell counts in the airways as a distinguishing trait. Neutrophilic inflammation is a hallmark of another type of allergic airway pathology , hypersensitivity pneumonitis. Considered as an immune counterpart of asthma, hypersensitivity pneumonitis is a prototypical type-III allergic inflammatory reaction involving the alveoli and lung interstitium, steered by Th 1 cells and IgG and, in its chronic form, accompanied by fibrosis. Although pathologically very different and commonly approached as separate disorders, as discussed in this review, clinical studies as well as data from animal models reveal undeniable parallels between both airway diseases. Danger signaling elicited by the allergenic agent or by accompanying microbial patterns emerges as critical in enabling immune sensitization and in determining the type of sensitization and ensuing allergic disease. On this basis , we propose that asthma allergens cause severe noneosinophilic asthma because of sensitization in the presence of hypersensitivity pneumonitis-promoting danger signaling.

Alternatively activated macrophages engage in homotypic and heterotypic interactions through IL-4 and polyamine-induced E-cadherin/catenin complexes

“…20 This approach results in an increase in IL-4 (similar to asthmatic mice) but an even higher increase in IFN-␥ in BALF ( Figure 6A). Recapitulating our in vitro findings ( Figure 1A), IFN-␥ counteracts the IL-4 effect in vivo, as no induction of Cdh1 mRNA and E-cadherin protein is detected during hypersensitivity pneumonitis ( Figure 6B-C).…”

“…Next, mice were challenged at day 21 and 22 for 30 minutes with aerosols, consisting of grade 3 OVA in PBS. 19,20 Twenty hours later, mice were killed and bronchoalveolar leukocytes (BALs) were collected by PBS rinsing of the lungs. IL-4 and interferon-␥ (IFN-␥) concentrations in BAL fluid were measured using Bio-plex (Bio-Rad).…”

“…Sensitization of C57BL/6 mice with OVA in Alum adjuvant, followed by OVA aerosols, triggers allergic airway inflammation, 20 akin to moderate asthma associated with increased levels of IL-4, but not IFN-␥, in the bronchoalveolar lavage fluid (BALF; Figure 6A). In this model, both monocyte-derived macrophages and dendritic cells (DCs) were shown to regulate the lung pathology.…”

Precarious Balance: Th17 Cells in Host Defense

“…For example, deficiency in IL-17 inhibits the development of a canonical form of hypersensitivity pneumonitis (40,84), a set of pulmonary disorders that results from chronic exposure to inhaled antigen, including Saccharopolyspora rectivirgula and other pathogenic bacteria (5). Likewise, animal models of allergen-induced airway and contact hypersensitivity suggest that the hyperreactivity of the Th17 lineage toward microbial antigens and homologous endogenous ligands contributes to pathology (64,71,92,96).…”

Mycobacterial hypersensitivity pneumonitis requires TLR9-MyD88 in lung CD11b+ CD11c+ cells

“…Saccharopolyspora rectivirgula) proliferating in damp hay [29][30][31]. Using the mouse S. rectivirgula-induced farmer's lung model, the role of Th1 CD4+ lymphocytes and the involvement of cellular and humoral adaptive immunity have been studied and moderately well documented [32][33][34][35][36][37][38].…”