The purpose of this study was to explore whether repeated exposure to aerosolized ovalbumin (OVA) in the context of local expression of GM-CSF can initiate a Th2-driven, eosinophilic inflammation in the airways. On day -1, Balb/c mice were infected intranasally with an adenovirus construct expressing GM-CSF (Ad/GM-CSF). From day 0 to day 9 mice were exposed daily to an OVA aerosol. Mice exposed to OVA alone did not show any evidence of airway inflammation. Mice receiving both Ad/GM-CSF and aerosolized OVA exhibited marked airway inflammation characterized by eosinophilia and goblet cell hyperplasia. Migration of eosinophils into the airway was preceded by a rise in IL-5 and IL-4. Both IL-5 and class II MHC were critically required to generate airway eosinophilia. After resolution, airway eosinophilia was reconstituted after a single OVA exposure. Flow cytometric analysis of dispersed lung cells revealed an increase in macrophages and dendritic cells expressing B7.1 and B7.2, and expansion of activated (CD69-expressing) CD4 and CD8 T cells in mice exposed to OVA and Ad/GM-CSF. Our data indicate that expression of GM-CSF in the airway compartment increases local antigen presentation capacity, and concomitantly facilitates the development of an antigen-specific, eosinophilic inflammatory response to an otherwise innocuous antigen.
M R Stämpfli, R E Wiley, G S Neigh, B U Gajewska, X F Lei, D P Snider, Z Xing, M Jordana
Title and authors | Publication | Year |
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GM-CSF-Licensed CD11b+ Lung Dendritic Cells Orchestrate Th2 Immunity to Blomia tropicalis
Q Zhou, AW Ho, A Schlitzer, Y Tang, KH Wong, FH Wong, YL Chua, V Angeli, A Mortellaro, F Ginhoux, DM Kemeny |
Journal of immunology (Baltimore, Md. : 1950) | 2014 |
Allergen Ligands in the Initiation of Allergic Sensitization
WR Thomas |
Current Allergy and Asthma Reports | 2014 |
Alveolar macrophages are sentinels of murine pulmonary homeostasis following inhaled antigen challenge
SA Mathie, KL Dixon, SA Walker, V Tyrrell, M Mondhe, VB O'Donnell, LG Gregory, CM Lloyd |
Allergy | 2014 |
Pleural innate response activator B cells protect against pneumonia via a GM-CSF-IgM axis
GF Weber, BG Chousterman, I Hilgendorf, CS Robbins, I Theurl, LM Gerhardt, Y Iwamoto, TD Quach, M Ali, JW Chen, TL Rothstein, M Nahrendorf, R Weissleder, FK Swirski |
Journal of Experimental Medicine | 2014 |
A GM-CSF/IL-33 pathway facilitates allergic airway responses to sub-threshold house dust mite exposure
A Llop-Guevara, DK Chu, TD Walker, S Goncharova, R Fattouh, JS Silver, CL Moore, JL Xie, PM O'Byrne, AJ Coyle, R Kolbeck, AA Humbles, MR Stämpfli, M Jordana |
PloS one | 2014 |
A GM-CSF/IL-33 Pathway Facilitates Allergic Airway Responses to Sub-Threshold House Dust Mite Exposure
A Llop-Guevara, DK Chu, TD Walker, S Goncharova, R Fattouh, JS Silver, CL Moore, JL Xie, PM O’Byrne, AJ Coyle, R Kolbeck, AA Humbles, MR Stämpfli, M Jordana, HW Chu |
PloS one | 2014 |
Molecular mechanisms and physiology of disease
N Maulik, T Karagiannis |
2014 |