Th2 Mediated Airway Diseases Strongly Linked to Fungal T Cell Memory

Paul Porter, Chu-Lin Tsai, Martin Citardi, Samer Fakhri, David B. Corry, Amber U. Luong

Abstract: 

Rationale

The role of fungi in the pathophysiology of T helper cell type 2 (Th2)-dependent airway diseases remains controversial. We hypothesized that pathogenic fungi and Th2 cell memory to fungi would be commonly associated with Th2 airway diseases supporting its role in these chronic inflammatory conditions.

Methods

Sinus and bronchoalveolar lavage fluid and peripheral blood were collected from 70 patients undergoing medically-indicated sinus surgery. Patients were characterized as Th2 airway disease (chronic rhinosinusitis (CRS) with nasal polyp and/or asthma) or without Th2 airway disease (CRS without nasal polyps or no CRS or no asthma). Lavage fluids were reduced with dithiothreitol to remove respiratory mucus and plated on Sabouraud’s agar. Isolated peripheral blood mononuclear cells were challenged with either a panel of 9 common fungal antigens (N=48) or antigens prepared from specific fungi isolated from patients’ lavage fluid (N=11). Number of fungus-specific IL-4-producing Th2 cells were determined by an ELISpot assay.

Results

Of the 70 fungal cultures, 71% (34 of 48) while 23% (5 of 22) were positive in patients with and without Th2 airway disease, respectively (P<0.001). Despite fungal presence in the airway, 0 of 21 (0%) of non-Th2-associated disease versus 20 of 27 (74%) of Th2-associated disease patients were IL-4 responsive to the fungal panel (P<0.001). Similarly, 0 of 4 (0%) versus 6 of 7 (86%) manifested fungus-specific IL-4 reactivity to the specific fungal antigen found within patient’s lavage fluid (P<0.000).

Conclusions

The presence of Th2-mediated airway diseases correlated strongly with fungal-specific IL-4 memory responses, supporting fungi in the pathophysiology of Th2-mediated airway diseases.

Journal of Allergy and Clinical Immunology, Vol. 131, Issue 2, AB203

http://dx.doi.org/10.1016/j.jaci.2012.12.1391

abstract No: 

724
    • AAAAI 2013 (69th)