Long-Term Exposure to House Dust Mite Leads to the Suppression of Allergic Airway Disease Despite Persistent Lung Inflammation.
BACKGROUND
Allergic asthma is a major cause of worldwide morbidity and results from inadequate immune regulation in response to innocuous, environmental antigens. The need exists to understand the mechanisms that promote nonreactivity to human-relevant allergens such as house dust mite (HDM) in order to develop curative therapies for asthma. The aim of our study was to compare the effects of short-, intermediate- and long-term HDM administration in a murine asthma model and determine the ability of long-term HDM exposure to suppress allergic inflammation.


METHODS
C57BL/6 mice were intranasally instilled with HDM for short-term (2 weeks), intermediate-term (5 weeks) and long-term (11 weeks) periods to induce allergic airway disease (AAD). The severity of AAD was compared across all stages of the model via both immunological and pulmonary parameters.


RESULTS
Short- and intermediate-term HDM exposure stimulated the development of AAD that included eosinophilia in the bronchoalveolar lavage fluid (BALF), pronounced airway hyperreactivity (AHR) and evidence of lung inflammation. Long-term HDM exposure promoted the suppression of AAD, with a loss of BALF eosinophilia and AHR despite persistent mononuclear inflammation in the lungs. Suppression of AAD with long-term HDM exposure was associated with an increase in both Foxp3+ regulatory T cells and IL-10-positive alveolar macrophages at the site of inflammation.


CONCLUSIONS
This model recapitulates the key features of human asthma and may facilitate investigation into the mechanisms that promote immunological tolerance against clinically relevant aeroallergens.
Department of Immunology, University of Connecticut Health Center, Farmington, Conn., USA.
Sonali J
SJ
Bracken
Alexander J
AJ
Adami
Steven M
SM
Szczepanek
Mohsin
M
Ehsan
Prabitha
P
Natarajan
Linda A
LA
Guernsey
Neda
N
Shahriari
Ektor
E
Rafti
Adam P
AP
Matson
Craig M
CM
Schramm
Roger S
RS
Thrall
D000818:Animals; D001249:Asthma / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000276:immunology*; D039981:Pyroglyphidae / Q000276:immunology*
D016207:Cytokines; D007074:Immunoglobulin G; D007073:Immunoglobulin E