Author:

Wiesner DL, Merkhofer RM, Ober C, Kujoth GC, Niu M, Keller NP, Gern JE, Brockman-Schneider RA, Evans MD, Jackson DJ, Warner T, Jarjour NN, Esnault SJ, Feldman MB, Freeman M, Mou H, Vyas JM, Klein BS

Date: 12 May 2020

Abstract:

Airway epithelium is the first body surface to contact inhaled irritants and report danger. Here, we report how epithelial cells recognize and respond to aeroallergen alkaline protease 1 (Alp1) of Aspergillus sp., because proteases are critical components of many allergens that provoke asthma. In a murine model, Alp1 elicits helper T (Th) cell-dependent lung eosinophilia that is initiated by the rapid response of bronchiolar club cells to Alp1. Alp1 damages bronchiolar cell junctions, which triggers a calcium flux signaled through calcineurin within club cells of the bronchioles, inciting inflammation. In two human cohorts, we link fungal sensitization and/or asthma with SNP/protein expression of the mechanosensitive calcium channel, TRPV4. TRPV4 is also necessary and sufficient for club cells to sensitize mice to Alp1. Thus, club cells detect junction damage as mechanical stress, which signals danger via TRPV4, calcium, and calcineurin to initiate allergic sensitization.

Link to DOI

Download the full article (Disclaimer)

This manuscript library of ~16,000 articles (1729-2024) related to Aspergillus and aspergillosis is intended for individual study only, and is provided as contribution to global understanding of the topic. Please refer to the publisher’s guidance about any other usage.

I understand (click to accept and view download link)

---