Streptococcus pneumoniae aminopeptidase N regulates dendritic cells that attenuates type-2 airway inflammation in murine allergic asthma.

BACKGROUND AND
PURPOSE: Epidemiological and experimental studies suggest that microbial exposure in early childhood is linked with reduced risk to suffer asthma. Thus microbial components with immunoregulatory capabilities might serve as a preventive strategy for allergic asthma. Recently, it was identified that Streptococcus pneumoniae aminopeptidase N (PepN) could suppress T cell effector function. We sought to investigate the effect of PepN on murine allergic asthma and elucidate the underlying mechanism. EXPERIMENTAL APPROACH: The effects of intranasal administration of PepN during or before sensitization were examined in ovalbumin (OVA)-induced murine allergic asthma. The roles of CD11b+ dendritic cells in PepN treated OVA-induced allergic asthma were evaluated by flow cytometry, cytokines detection and adoptive transfer. Moreover, the numbers of lung type 2 innate lymphoid cells (ILC2s) were also detected. KEY
RESULTS: Administration of PepN during or before sensitization attenuated type-2 airway inflammation (eosinophilia, mucus hypersecretion, Th2 cytokines production and IgE production) in allergic asthma mice. PepN reduced lung accumulation of CD11b+ dendritic cells, which was accompanied by diminished dendritic cell-attracting chemokine CCL20 production as well as CCL17 and CCL22, which are Th2-cell chemokines predominantly produced by CD11b+ dendritic cells. Adoptive transfer of BM-derived CD11b+ dendritic cells abolished the inhibitory effect of PepN on OVA-induced type-2 airway inflammation. The numbers of lung ILC2s were decreased in asthmatic mice receiving PepN. CONCLUSION AND IMPLICATIONS: PepN alleviated type-2 inflammation in OVA-induced allergic asthma mice, which was mediated by regulation of lung CD11b+ dendritic cells. Our study provides a novel strategy for the prevention of allergic asthma.