Endotoxin Exposure during Sensitization to Blomia tropicalis Allergens Shifts TH2 Immunity Towards a TH17-Mediated Airway Neutrophilic Inflammation: Role of TLR4 and TLR2

Author(s)

Barboza, Renato ^[1] ; Saraiva Camara, Niels Olsen ^[1] ; Gomes, Eliane ^[1] ; Sa-Nunes, Anderson ^[1] ; Florsheim, Esther ^[1] ; Mirotti, Luciana ^[1] ; Labrada, Alexis ^[2] ; Alcantara-Neves, Neuza Maria ^[3] ; Russo, Momtchilo ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508 Sao Paulo - Brazil

^[2] Ctr Nacl Biopreparados, Dept Alergenos, Havana - Cuba

^[3] Univ Fed Bahia, Inst Ciencias Saude, BR-41170290 Salvador, BA - Brazil

• Document type: Journal article
• Source: PLoS One; v. 8, n. 6 JUN 21 2013.
• Web of Science Citations: 22

Abstract

Experimental evidence and epidemiological studies indicate that exposure to endotoxin lipopolysaccharide (eLPS) or other TLR agonists prevent asthma. We have previously shown in the OVA-model of asthma that eLPS administration during alum-based allergen sensitization blocked the development of lung TH2 immune responses via MyD88 pathway and IL-12/IFN-gamma axis. In the present work we determined the effect of eLPS exposure during sensitization to a natural airborne allergen extract derived from the house dust mite Blomia tropicalis (Bt). Mice were subcutaneously sensitized with Bt allergens co-adsorbed onto alum with or without eLPS and challenged twice intranasally with Bt. Cellular and molecular parameters of allergic lung inflammation were evaluated 24 h after the last Bt challenge. Exposure to eLPS but not to ultrapure LPS (upLPS) preparation during sensitization to Bt allergens decreased the influx of eosinophils and increased the influx of neutrophils to the airways. Inhibition of airway eosinophilia was not observed in IFN-gamma deficient mice while airway neutrophilia was not observed in IL-17RA-deficient mice as well in mice lacking MyD88, CD14, TLR4 and, surprisingly, TLR2 molecules. Notably, exposure to a synthetic TLR2 agonist (PamCSK4) also induced airway neutrophilia that was dependent on TLR2 and TLR4 molecules. In the OVA model, exposure to eLPS or PamCSK4 suppressed OVA-induced airway inflammation. Our results suggest that B. tropicalis allergens engage TLR4 that potentiates TLR2 signaling. This dual TLR activation during sensitization results in airway neutrophilic inflammation associated with increased frequency of lung TH17 cells. Our work highlight the complex interplay between bacterial products, house dust mite allergens and TLR signaling in the induction of different phenotypes of airway inflammation. (AU)

• FAPESP's process: 11/17880-8 - Toll-like receptors and NOD-like receptors in pregnancy-associated malaria pathogenesis: effects and mechanisms
• Grantee: Renato Barboza
• Support Opportunities: Scholarships in Brazil - Post-Doctoral