Journal of Clinical and Cellular Immunology
Open Access

Mouse pathway biology models: Investigating the biology of Alternaria alternata induced lung inflammation in the mouse - role of ILC2 and Th2 cytokines

International Conference on Innate Immunity

July 20-21, 2015 Barcelona, Spain

Milenko Cicmil

Posters-Accepted Abstracts: J Clin Cell Immunol

Abstract :

Alternaria alternata (A. alternate) is a fungal allergen associated with exacerbations and death in asthmatic patients. To gain a better understanding of the role of immunomodulatory mechanisms in Th2 mediated inflammation, we established a murine model of A. alternata induced lung inflammation. Intratracheal instillation of A. alternata induces IL-33 release from lung epithelium, triggering activation of innate lymphoid cells (ILC2s), and subsequent release of the potent Th2 cytokines IL-5 and IL-13 eventually leading to BALf eosinophilia. In this study, we established a time course for BALf eosinophilia following A. alternata challenge and examined the effects of neutralizing antibodies on Th2 mediated inflammation. We demonstrated that anti-IL-5 and anti-IL-13 antibodies inhibit eosinophilic inflammation (91% ± 2 and 65% ± 6; mean ± SEM, respectively), while anti-IL-4 and anti-TSLP treatment had no significant effect on eosinophil levels. In addition, using flow cytometry, we detected a significant increase in ILC2s presence in the lung, following A. alternata challenge. Finally, our mRNA expression profiling indicate a time dependent induction for a range of immunomodulators including PD-1, PD-L1, PD-L2 and TIGIT, with levels reaching peak at 72 to 96 hours post challenge. The data obtained suggest that using human relevant allergen in rodent settings may provide useful tool to study the role of ILC2s and immunomodulatory targets following A. alternata challenge.