Airway house dust extract exposures modify allergen-induced airway hypersensitivity responses by TLR4-dependent and independent pathways.

Abstract

TLR ligands and other allergen-nonspecific immunostimulatory molecules are ubiquitous in ambient air and have profound modulatory activities in animal models of allergic asthma. However, several of these molecules have been shown to promote exaggerated Th2-biased airway hypersensitivity responses (AHRs), whereas others attenuate the asthmatic phenotype. Therefore, it has proven difficult to extrapolate experimental results with purified molecules toward a more general understanding of the allergen-nonspecific immunomodulatory influence of living environments on the natural history of allergic asthma. These investigations determined how regular and intermittent airway exposures to an unpurified, but sterile house dust extract standard (HDEst) affected the OVA-specific AHR and immune status of previously Th2-sensitized mice. Low-dose daily and high-dose intermittent HDEst exposures modulated ongoing AHRs considerably, reducing eosinophil recruitment and methacholine responsiveness, while increasing neutrophilic inflammation. However, only daily airway delivery of low-dose HDEst attenuated OVA-specific Th2 cytokine production and Th2-biased AHRs to allergen challenge 1 mo later. Finally, whereas LPS mimicked many of the immunomodulatory characteristics of HDEst in this murine asthma model, daily airway HDEst delivery was highly effective in attenuating the AHR of OVA/alum-sensitized TLR4-deficient mice. Taken together, these investigations provide direct evidence that living environments contain allergen-nonspecific immunostimulatory molecules that influence the airway hypersensitivity status of allergen-sensitized mice by TLR4-dependent and independent mechanisms.

• Authors: Diane Lam, Nicholas Ng, Steve Lee, Glenda Batzer, Anthony A Horner
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 181 Issue 4 Pg. 2925-32 (Aug 15 2008) ISSN: 1550-6606 [Electronic] United States
• PMID: 18684984 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Adjuvants, Immunologic
• Allergens
• Dust
• Tlr4 protein, mouse
• Toll-Like Receptor 4
• Ovalbumin

Topics

• Adjuvants, Immunologic (administration & dosage, physiology)
• Allergens (administration & dosage, immunology)
• Animals
• Bronchial Hyperreactivity (immunology, metabolism)
• Dust (immunology)
• Female
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Ovalbumin (administration & dosage, immunology)
• Respiratory Hypersensitivity (immunology, metabolism)
• Respiratory Mucosa (immunology, metabolism)
• Signal Transduction (genetics, immunology)
• Th2 Cells (immunology, metabolism)
• Toll-Like Receptor 4 (deficiency, genetics, physiology)