Abstract
Immunological memory is a cardinal feature of the immune system. The intestinal mucosa is the primary exposure and entry site of infectious organisms. For an effective and long-lasting safeguard, a robust immune memory system is required, especially by the mucosal immunity. It is well known that tissue-resident memory T cells (Trms) provide a first response against infections reencountered at mucosal tissues surfaces, where they accelerate pathogen clearance. However, their function in intestinal immunization remains to be investigated. Here, we report enhanced local mucosal and systemic immune responses through oral administration of H9N2 influenza whole inactivated virus (H9N2 WIV) plus Bacillus subtilis spores. Subsequently, H9N2 WIV plus spores led to the generation of CD103+ CD69+ Trms, which were independent of circulating T cells during the immune period. Meanwhile, we also found that Bacillus subtilis spores could stimulate Acrp30 expression in 3T3-L1 adipocytes. Moreover, spore-stimulated adipocyte supernatant also upregulated the expression of intercellular adhesion molecule-1 (ICAM1) in dendritic cells (DCs). Furthermore, the proportion of HA-tetramer+ cells was severely curtailed upon suppressed ICAM1 expression, which also depended on HA-loaded DCs. Taken together, our data demonstrated that spore-promoted H9N2 WIV induced an immune response by enhancing Trms populations, which were associated with the activation of ICAM1 in DCs.
Highlights
Immunological memory is a cardinal feature of the immune system
We found that serum collected from different groups of mice at 21 days and 49 days showed a powerful ability to inhibit hemagglutination by 4-HA units of H9N2 compared with antigen alone (Figure 1D) Lastly, lymphocytes from the spleen and mesenteric lymph node (MLN) of mice 21 days and 49 days post immunization were restimulated with H9N2 WIV in vitro
Since a previous study found that Acrp30 receptor signaling in dendritic cells (DCs) can interfere with T-cell functions, we investigated whether spore-stimulated medium could increase intercellular adhesion molecule-1 (ICAM1) expression on
Summary
Immunological memory is a cardinal feature of the immune system. The intestinal mucosa is the primary exposure and entry site of infectious organisms. It is well known that tissue-resident memory T cells (Trms) provide a first response against infections reencountered at mucosal tissues surfaces, where they accelerate pathogen clearance. Their function in intestinal immunization remains to be investigated. The proportion of HA-tetramer+ cells was severely curtailed upon suppressed ICAM1 expression, which depended on HA-loaded DCs. Taken together, our data demonstrated that spore-promoted H9N2 WIV induced an immune response by enhancing Trms populations, which were associated with the activation of ICAM1 in DCs. AIV, has become a significant threat to humans and animals [1,2]. Bacillus subtilis spores, acting as adjuvants, can strongly induce immune responses against pathogens, especially by modulating intestinal mucosal immunity by evoking tissue-resident memory T cells (Trms) [7,8,9]. Previous studies found that Bacillus subtilis spores can stimulate the secretion of cytokines during innate immune signaling, which is indispensable for an efficient induction published maps and institutional affiliations
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