Bacillus subtilis spore induces efficient generation of memory T cells via ICAM-1 expression on dendritic cells

Abstract

The intestinal mucosa is the primary exposure and entry site of infectious organisms. Tissue-resident memory T cells (Trms) is an important first line of defense against infection in mucosal tissues, their function in intestinal immunization remains to be investigated. Here, we reported that the levels of local mucosal and systemic immune responses were enhanced through oral immunization with H9N2 whole inactivated virus (H9N2 WIV) plus spore. Subsequently, H9N2 WIV plus spore led to the generation of CD103+CD69+ Trms, which was independent of circulating T cells during the immune period. Meanwhile, we also found that Bacillus subtilis spore can stimulate Acrp30 expression in 3T3-L1 adipocytes. Moreover, adipocyte supernatant or spore also upregulated intercellular adhesion molecule-1 (ICAM-1) expression on dendritic cells (DCs) (P<0.01). Furthermore, the proportion of HA-tetramer+cells was severely curtailed when ICAM-1 expression was suppressed, which was also dependent on HA-loaded DCs. Taken together, our data demonstrated that spore promoted the immune response by stimulating Trms, which were associated with activation of ICAM-1 in DCs. Author summaryTaken together, Bacillus subtilis spore combined with H9N2 WIV enhanced the mucosal antibody response and induced efficient intestinal-resident memory T cells. Then we demonstrated that spore can induce memory T cell formation through an ICAM-1-mediated contact of a dendritic cell (DC)-derived mechanism. Further, our findings indicated that Acrp30 from adipocytes induced by spore might increase ICAM-1 expression on DCs, which might provide new insight into the significance of adipocyte metabolism related molecules in regulating immunological memory T cells.