The effect of mouse naturalization on the development of lung mast cells and allergic reactions 3406

Description Mast cells are major effector cells responsible for allergic inflammation. Specific pathogen-free (SPF) laboratory mice are profoundly deficient in lung parenchymal mast cells, which contrasts sharply with an abundant presence of these cells in human lungs. We first reported that lung mast cells could be identified in free-living wild mice, suggesting that wild mice may better mimic human asthmatic responses. Given the challenges of using wild mice for routine experimental work, we proposed a “naturalization” approach to repopulate mast cells in the lung tissues of conventional laboratory SPF mice. Thus, laboratory mice were housed on bedding materials sourced regularly from a chicken farm, a habitat for wild rodents, in suburban Hong Kong. Laboratory mice exposed to this “dirty” environment during the neonatal period, but not adulthood, exhibited gut microbiota normalization toward that of wild mice. Notably, these neonatally naturalized mice developed lung parenchymal mast cells and could be induced to exhibit enhanced asthmatic responses, characterized by increased infiltration of neutrophils in the airway secretions, likely because of heightened mast cell activity. In contrast, it is difficult to induce asthmatic responses with a neutrophilic component using conventional SPF mice. Our naturalized mouse asthma model more closely mimics human neutrophilic asthma, which may provide a tool for more reliably screening drug candidates for treating human neutrophilic asthma.