Multicomponent Pathogen-Mimicking Nanoparticles Induce Intestinal Immune Responses against Paratuberculosis.

Given the worldwide problem posed by enteric pathogens, the discovery of safe and efficient intestinal adjuvants combined with novel antigen delivery techniques is essential to the design of mucosal vaccines. In this work, we designed poly (lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) to codeliver all-trans retinoic acid (atRA), novel antigens, and CpG. To address the insolubility of the intestinal adjuvant atRA, we utilized PLGA to encapsulate atRA and form a "nanocapsid" with polydopamine. By leveraging polydopamine, we adsorbed the water-soluble antigens and the TLR9 agonist CpG onto the NPs' surface, resulting in the pathogen-mimicking PLPCa NPs. In this study, the novel fusion protein (HBf), consisting of the Mycobacterium avium subspecies paratuberculosis antigens HBHA, Ag85B, and Bfra, was coloaded onto the NPs. In vitro, PLPCa NPs were shown to promote the activation and maturation of bone marrow-derived dendritic cells. Additionally, we found that PLPCa NPs created an immune-rich microenvironment at the injection site following intramuscular administration. From the results, the PLPCa NPs induced strong IgA levels in the gut in addition to enhancing powerful systemic immune responses. Consequently, significant declines in the bacterial burden and inflammatory score were noted in PLPCa NPs-treated mice. In summary, PLPCa can serve as a novel and safe vaccine delivery platform against gut pathogens, such as paratuberculosis, capable of activating both systemic and intestinal immunity.

Melatonin mediates monochromatic light-induced expression of somatostatin in the hypothalamus and pituitary of chicks.

Melatonin (MEL) plays an important role in regulating growth and development of organisms and the cellular metabolism. This study was conducted to explore the role of MEL in mediating monochromatic light-induced secretion of somatostatin (SST) in the hypothalamus and pituitary in chicks. Pinealectomy models of newly hatched broilers were exposed to white (WL), red (RL), green (GL), and blue (BL) lights. The results showed that SST immunoreactive neurons and fibers were distributed in the hypothalamus. SST and SST receptor 2 (SSTR2) mRNA and protein levels in the hypothalamus and pituitary were higher in chicks exposed to RL than in chicks exposed to GL and BL. However, after pinealectomy, the mRNA and protein levels of SST and SSTR2 in the hypothalamus and pituitary in the different light groups were increased, and the differences between the groups disapeared. The expression trend of SSTR5 mRNA in the pituitary was the idential to that of SSTR2 mRNA in the pituitary. In vitro, exogenous SST inhibited growth hormone (GH) secretion, and selective antogonists of SSTR2 and SSTR5 promoted GH secretion. Selective antogonists of the melatonin receptor 1b (Mel1b) and Mel1c increased the relative concentrations of SST in the adenohypophysis cells. These results indicated that monochromatic light affects the expression of SST in chick hypothalamus and pituitary. MEL, via Mel1b and Mel1c, decreased SST secretion under GL, which was associated with the inhibition of SST, SSTR2, and SSTR5 in adenohypophysis cells.