title: Innate type 2 response to Alternaria extract enhances ryegrass-induced lung inflammation.
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 after Alternaria extract exposure in ryegrass-challenged mice. Innate immune challenges with Alternaria 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.
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, Calif., USA.
authors.forename: Hee-Kyoo
authors.initials: HK
authors.lastname: Kim
authors.forename: Sean
authors.initials: S
authors.lastname: Lund
authors.forename: Rachel
authors.initials: R
authors.lastname: Baum
authors.forename: Peter
authors.initials: P
authors.lastname: Rosenthal
authors.forename: Naseem
authors.initials: N
authors.lastname: Khorram
authors.forename: Taylor A
authors.initials: TA
authors.lastname: Doherty
mesh_terms: D000485:Allergens / Q000276:immunology; D000528:Alternaria / Q000276:immunology*; D060487:Alternariosis / Q000150:complications / Q000276:immunology*; D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology; D052179:Antigens, Plant / Q000008:administration & dosage / Q000276:immunology; D001249:Asthma / Q000150:complications / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007114:Immunization; D008129:Lolium / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology; D011014:Pneumonia / Q000150:complications / Q000276:immunology*; D011058:Pollen / Q000276:immunology; D012129:Respiratory Function Tests; D018418:Th2 Cells / Q000276:immunology; D014887:Weather
chemical_list: D000485:Allergens; D000946:Antigens, Fungal; D052179:Antigens, Plant; D016207:Cytokines