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 thatStreptococcus pneumoniaeaminopeptidase 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.