Innate immune activation in neutrophilic asthma and bronchiectasis

Jodie L Simpson ¹, Terry V Grissell ¹, Jeroen Douwes ², Rodney J Scott ³, Michael J Boyle ⁴ and Peter G Gibson ^1*

¹ School of Medicine and Public Health, The University of Newcastle, NSW, Australia
² Centre for Public Health Research, Massey University, New Zealand
³ School of Biomedical Science, The University of Newcastle, NSW, Australia
⁴ Immunology and Infectious Diseases, John Hunter Hospital, Australia

^* To whom correspondence should be addressed. E-mail: peter.gibson{at}hnehealth.nsw.gov.au.

Accepted 28 June 2006

Abstract

Background: The role of the innate immune system in the pathogenesis of asthma is unclear. Activation of innate immune receptors in response to bacterial lipopolysaccharide, virus infection and particulate matter, triggers a pre-programmed inflammatory response, which involves IL-8 and neutrophil influx. The inflammatory response in asthma is heterogeneous and this study tested the hypothesis that innate immune activation may be a relevant inflammatory mechanism in neutrophilic asthma where IL-8 levels are increased.

Methods: Induced sputum was obtained from non-smoking adults with asthma (n=49), healthy controls (n=13) and a positive reference group with bronchiectasis (n=9). Subjects with asthma were classified into inflammatory subtypes using induced sputum cell counts. Sputum was examined for mRNA expression of the innate immune receptors TLR2, TLR4 and CD14, and inflammatory cytokines. A separate sputum portion was dispersed and supernatant assayed for surfactant protein A, IL-8, soluble CD14 and endotoxin.

Results: Expression of innate immune receptors was increased in bronchiectasis and in subjects with neutrophilic asthma compared to other asthma subtypes and healthy controls. There was increased expression of the receptors TLR2, TLR4 and CD14 as well as the pro-inflammatory cytokines IL-8 and IL-1. Subjects with neutrophilic asthma had higher airway levels of endotoxin compared to other groups studied.

Conclusion: There is evidence of activation of the innate immune system in asthma, which results in the production of pro-inflammatory cytokines, and may contribute to the pathogenesis of neutrophilic asthma.

Keywords: asthma, endotoxin, interleukin-8, pulmonary associated surfactant protein A, toll-like receptors

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