Innate Type 2 Response to Alternaria Extract Enhances Ryegrass-Induced Lung Inflammation

Vol. 163, No. 2, 2014

Issue release date: February 2014

Editor's Choice -- Free Access

Int Arch Allergy Immunol 2014;163:92-105
(DOI:10.1159/000356341)

Fulltext PDF (630 Kb)

Original Paper

Kim H.-K.a, b · Lund S.a · Baum R.a · Rosenthal P.a · Khorram N.a · Doherty T.A.a  aDepartment of Medicine, University of California San Diego, La Jolla, Calif., USA; bDepartment of Internal Medicine, Kosin University College of Medicine, Busan, Korea  Corresponding Author

---

 Outline

• Key Words

• Abstract
• Introduction
• Materials and Methods
• Mice
• Ryegrass and Alternaria Airway Inflammation Models
• Lung Processing and BAL Cellular Analysis
• Flow Cytometry
• BAL and Serum ELISA
• Periodic Acid-Schiff Analysis
• Inflammation Index
• Pulmonary Function Testing
• Statistical Analysis
• Results
• Development of a Ryegrass-Induced Lung Inflammation Model
• Alternaria Extract Induces ILC2 Proliferation and Recruitment of Eosinophils and Th2 Cells
• A Single Alternaria Extract Exposure prior to Ryegrass Challenges Enhances Lung Inflammation
• Alternaria Extract Induces Airway Eosinophil, Th2 Cell, and ILC2 Recruitment
• Alternaria Extract Exposure after Ryegrass Challenges Increases Airway Eosinophilia
• Discussion
• Acknowledgments
• References

• Author Contacts
• Article Information
• Publication Details
• Drug Dosage / Copyright

---

  Key Words


• Alternaria
• Asthma
• Ryegrass
• Thunderstorm asthma
• ILC2


---

  Abstract

Background: Exposure to the fungal allergen Alternaria alternata as well as ryegrass pollen has been implicated in severe asthma symptoms during thunderstorms. We have previously shown that Alternaria extract induces innate type 2 lung inflammation in mice. We hypothesized that the innate eosinophilic response to Alternaria extract may enhance lung inflammation induced by ryegrass. Methods: Mice were sensitized to ryegrass allergen and administered a single challenge with A. alternata extract before or after final ryegrass challenges. Levels of eosinophils, neutrophils, Th2 cells, innate lymphoid cells (ILC2), interleukin (IL)-5 and IL-13 in bronchoalveolar lavage (BAL) as well as inflammation and mucus were assessed. Results: Mice receiving ryegrass sensitization and challenge developed an eosinophilic lung response. A single challenge with Alternaria extract given 3 days before or 3 days after ryegrass challenges resulted in increased eosinophils, peribronchial inflammation and mucus production in the airways compared with ryegrass-only challenges. Type 2 ILC2 and Th2 cell recruitment to the airways was increased afterAlternaria extract exposure in ryegrass-challenged mice. Innate immune challenges withAlternaria extract induced BAL eosinophilia, Th2 cell recruitment as well as ILC2 expansion and proliferation. Conclusions: A single exposure to Alternaria extract in ryegrass-sensitized and -challenged mice enhances the type 2 lung inflammatory response, including airway eosinophilia, peribronchial infiltrate, and mucus production, possibly through Th2 cell recruitment and ILC2 expansion. If translated to humans, exposure to both grass pollen and Alternaria may be a potential cause of thunderstorm-related asthma.

Fulltext PDF (630 Kb)