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2630526 
Journal Article 
Abstract 
House dust mite exposure induces direct non-allergic inflammation in rodent airways: role of the innate immune system 
Eltom, S; Raemdonck, K; De Alba, J; Belvisi, MG; Birrell, MA 
2010 
Yes 
American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 
181 
A2837 
English 
WOS:000208771001749 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
Introduction: Exposure to house dust mite (HDM) allergen has been linked to asthma pathogenesis. In-house data has previously established that a single challenge with HDM (Derp1) leads to an increase in inflammatory cells in the bronchoalveolar lavage fluid (BALF) from non-sensitised mice. This data challenges the premise that HDM exposure to mice induces a purely “allergic” phenotype. Recent studies have shown that HDM-driven inflammation involves TLR4 activation eg. (PAMPs), and other in vivo studies have suggested a functional role for ATP (DAMPs) in asthmatic airway inflammation (Hammad et al. 2009, Idzko et al. 2007). We hypothesise that both PAMPs and DAMPs (eg. HDM-induced ATP release leading to P2X7-induced inflammasome activation) are required to initiate the innate immune response in vivo mediated by HDM exposure.

Methods: C57BL/6 mice (18-24g) were challenged once intratracheally with vehicle (saline) or HDM (Derp1 25µg). BALF and lung tissue samples were collected and the associated inflammatory response evaluated 48 hours after challenge.

Results: Our data demonstrates that mice challenged with a high dose of HDM (25μg) show a significant increase in BALF total cells (218.8±46.15 x 10^3 cells/ml; p<0.05) compared to saline challenged animals (86.25±10.25 x 10^3 cells/ml). HDM challenge also exhibited significant increases in eosinophils (saline 0.75±0.44 vs. HDM challenged 17.33±5.98 x 10^3 cells/ml; p<0.05), neutrophils (saline 1.86±0.93 vs. HDM challenged 314.4±82.2 x 10^3 cells/ml; p<0.05) and lymphocytes (saline 9.70±6.37 vs. HDM challenged 59.37±12.54 x 10^3 cells/ml; p<0.05) when compared to their respective saline controls. In order to establish what component may be driving this response the following experiments were performed. Increases in BALF total cells in response to HDM challenge (saline 81.6±7 vs. HDM challenged 1019±92 x 10^3 cells/ml; p<0.05) were significantly attenuated in animals challenged with protease inactivated HDM (298.2±102.2 x 10^3 cells/ml; p<0.05), in P2X7 KO mice (702.5±51.75 x 10^3 cells/ml; p<0.05), in TLR4 KO mice (510±77.48 x 10^3 cells/ml; p<0.05) and in response to a steroid (313.3±71.26 x 10^3 cells/ml; p<0.05).

Conclusion: This data suggests that the direct, non-allergic inflammation seen in response to HDM exposure in this model is dependent upon both P2X7 and TLR4 activation and protease activity. Further investigation of the complex underlying mechanisms responsible could further our understanding of HDM-induced inflammation.

Hammad et al. 2009. Nat Med. 2009 Apr;15(4):366-7.
Idzko et al. 2007. Nat Med. 2007 Aug;13(8):913-9. 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010