초록 |
Microbial pathogens present “danger” signals at the site of infection and confers protective immunity by inducing proinflammatory cytokines and mobilizing leukocytes. During microbial infection, pathogen associated molecular patterns (PAMPs) activate pattern recognition receptors (PRRs) expressed on innate immune cells, such as dendritic cells (DCs), leading to the production of proinflammatory cytokines, including IL-1β, IL-6, and IL-23, that promote the differentiation and stabilization of T helper 17 (Th17) cells. We have recently reported the development of Saccharomyces cerevisiae (S. cerevisiae) mannan-based nanocapsules (Mann-NC) for subcutaneous delivery of mRNA-based vaccines against cancer. We also demonstrate here that Mann-NC composed of mostly mannan (without any other cargo) is a potent nano-PAMP for Dectin-2 and TLR-4 activation and that intratumoral administration of Mann-NC generates robust Th17 responses in favor of antitumor effects. PAMP-PRR interaction is controlled by the geometry, nanoscale arrangement, and architecture of PAMP on Mann-NC for multivalent surface PAMP arrangement with structural flexibility for favorable PRR engagement. |