Aspergillus Fumigatus May Promote Th2 Activation By Suppression Of Interferon Signaling

S U N D A Y 478 Aspergillus Fumigatus May Promote Th2 Activation By Suppression Of Interferon Signaling Dr. Tetsuya Homma, MD, Mr. Bharat Bhushan, Dr. Atsushi Kato, PhD, Mr. James Norton, MS, Ms. Lydia Suh, BSc, Dr. Quan Sha, MD, PhD, Dr. Dave S. Gupta, MD, Dr. Robert P. Schleimer, PhD, FAAAAI; Department of Medicine, Division of Allergy-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, Department of Internal Medicine, Division of Respiratory Medicine and Allergology, Showa University School of Medicine, Tokyo, Japan, Division of Otolaryngology-Head and Neck Surgery, Ann & Robert H. Lurie Children’s Hospital of Chicago, Allergy and Immunology research center, Anhui Medical University, China, Department of Allergy Immunology, National Jewish Health, Denver, CO, Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL. RATIONALE: Aspergillus fumigatus(AF) infection and sensitization are common and promote respiratory diseases. Innate immune responses of bronchial epitheliums are known to play a key role in determination of T cell responses upon encounters with pathogens. To elucidate the impact of AF on human bronchial epitheliums, we hypothesized that AF can modulate the response of epithelium to favor a Th2 response. METHODS: A bronchial epithelial cell line (BEAS-2B) was stimulated with IFN-beta, poly I:C, IL-4, IL-17A and AF extract for 6 hours. Due to protease activity of the extract, we also examined the cell viability. Cells were collected to measure mRNA (RT-PCR) and supernatants were collected to measure protein (ELISA). Extract was fractionated by filtration based on molecular weight and heat treated for initial characterization of active compounds within the extract. Western blotting was performed to evaluate suppression of IFN-beta activated STAT-1 by AF. RESULTS: AF extract profoundly suppressed IFN-beta and poly I:C induced CXCL10 and BAFF in a dose dependent manner (69.2% reduction with the most concentrated extract, p 50kDa) retained the suppressive effect, but low molecular weight (LMW<50kDa) did not. The LMW extract treated cells had reduced viability at 48 hours (71.3% reduction, p<0.01) but the HMW extract had amodest effect (9.5% reduction) onviability. Importantly, IFNbeta induced phosphorylation of STAT-1 was inhibited by AF. CONCLUSIONS: Exposure of bronchial epithelial cells to AF extracts may suppress IFN-signaling and thus skew epithelial cells to promote Th2related allergic diseases such as CRS and asthma.