Modeling asthma in macaques: longitudinal changes in cellular and molecular markers

Question: Does systemic sensitization and chronic aeroallergen challenge in macaques replicate classical and emerging immunology and molecular pathology of human asthma? Methods: Macaques were immunized and periodically challenged over 2 years with house dust mite allergen (HDM). At key times, serum, bronchoalveolar lavage (BAL) and bronchial biopsies were assayed for genes, proteins, and lymphocyte subpopulations relevant to clinical asthma. Results: Immunization and periodic airway challenge induced changes in IgE, airway physiology, and eosinophilia consistent with chronic, dual phase asthma. Immunization increased IL-1β and IL-6 in serum, and IL-13 expression in BAL. Airway challenge increased early expression of IL-5, -6, -13, -19, and eotaxin; and variable late phase expression of IL-4, -5, -13 and TARC. CD4+ lymphocytes comprised 30% of the CD3+ cells in BAL, increasing to 50% in the late phase. NKT cells represented less than 2% of the CD3+ cells. Corticosteroid treatment reduced serum histamine levels, percentage of CD4+ cells, and MDC expression; while increasing CD3+ and CD8+ cells in BAL. Conclusion: Sensitization and periodic aeroallergen challenge of cynomolgus macaques results in physiological, cellular, molecular and protein phenotypes and therapeutic responses observed in human asthma, providing a model system useful in target and biomarker discovery and translational asthma research.