Bacterial lysate enhances protective mucosal immunity via increased expression of antimicrobial peptides

Polyvalent mechanical bacterial lysate (PMBL) has been reported to be effective in the prevention of common respiratory tract infections. PMBL are produced through a process that preserves the structure of the bacterial antigens and because of their immunogenic capabilities, increasing importance is given to its mechanism of action, not yet fully understood. Respiratory tract epithelial cells constitute a front-line physical barrier between the organism and the environment. They are able to sense pathogen associated molecular patterns and secrete a wide spectrum of protective factors. By using primary normal Human Bronchial Epithelial Cells (HBEpiCs), we observed that PMBL can improve epithelial barrier integrity via induction of adhesion molecules. Along with adhesion molecules, PMBL had a significant effect on epithelial cell proliferation increasing the expression of the autocrine growth factor Amphiregulin (AR). Moreover, treatment with PMBL promoted ex-novo gene expression of human beta-defensin 2 (HβD-2) on HBEpiCs and conferred them a direct antimicrobial activity. Epithelial cells are structural components of mucosal immunity that include also dendritic cells (DCs) and innate lymphoid cell-type 3 (ILC3s). PMBL induced IL-23 and IL-1β secretion by DCs that, in turn, activate ILC3s to produce IL-22, cytokine primarily involved in the induction of antimicrobial peptides (AMPs). Interestingly, IL-23 produced by DCs can also activate epithelial cells and lead to a boost of IL-22 production by ILC3s. Remarkably, HβD-2 and LL-37 AMPs can be induced in the saliva of normal subjects after administration of PMBL. Altogether, these results indicate that PMBL administration might support a critical barrier-protective immune pathway that originates from, and is orchestrated by airway epithelial cells and could be therapeutically exploited for the prevention of airway infections.