Defective respiratory tract immune surveillance in asthma : a primary causal factor in disease onset and progression

Holt, Patrick G., Strickland, Deborah H., Hales, Belinda J. and Sly, Peter D. (2014) Defective respiratory tract immune surveillance in asthma : a primary causal factor in disease onset and progression. Chest, 145 2: 370-378. doi:10.1378/chest.13-1341


Author Holt, Patrick G.
Strickland, Deborah H.
Hales, Belinda J.
Sly, Peter D.
Title Defective respiratory tract immune surveillance in asthma : a primary causal factor in disease onset and progression
Journal name Chest   Check publisher's open access policy
ISSN 0012-3692
1931-3543
Publication date 2014-02-01
Year available 2014
Sub-type Article (original research)
DOI 10.1378/chest.13-1341
Open Access Status Not Open Access
Volume 145
Issue 2
Start page 370
End page 378
Total pages 9
Place of publication Northbrook, IL, United States
Publisher American College of Chest Physicians
Language eng
Abstract The relative importance of respiratory viral infections vs inhalant allergy in asthma pathogenesis is the subject of ongoing debate. Emerging data from long-term prospective birth cohorts are bringing increasing clarity to this issue, in particular through the demonstration that while both of these factors can contribute independently to asthma initiation and progression, their effects are strongest when they act in synergy to drive cycles of episodic airways infl ammation. An important question is whether susceptibility to infection and allergic sensitization in children with asthma arises from common or shared defect(s). We argue here that susceptibility to recurrent respiratory viral infections, failure to generate protective immunologic tolerance to aeroallergens, and ultimately the synergistic interactions between infl ammatory pathways triggered by concomitant responses to these agents all result primarily from functional defi ciencies within the cells responsible for local surveillance for antigens impinging on airway surfaces: the respiratory mucosal dendritic cell (DC) network. The effects of these defects in DCs from children wtih asthma are accentuated by parallel attenuation of innate immune functions in adjacent airway epithelial cells that reduce their resistance to the upper respiratory viral infections, which are the harbingers of subsequent infl ammatory events at asthma lesion site(s) in the lower airways. An important common factor underpinning the innate immune functions of these unrelated cell types is use of an overlapping series of pattern recognition receptors (exemplifi ed by the Toll-like receptor family), and variations in the highly polymorphic genes encoding these receptors and related molecules in downstream signaling pathways appear likely contributors to these shared defects. Findings implicating recurrent respiratory infections in adult-onset asthma, much of which is nonatopic, suggest a similar role for defi cient immune surveillance in this phenotype of the disease.
Keyword Asthma
Causal factors
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Queensland Children's Medical Research Institute Publications
 
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