Abstract
The digestive tract is the entry site for transmissible gastroenteritis virus (TGEV). TGEV transmission can be prevented if local immunity is established with increased lymphocytes. The current parenteral mode of vaccination stimulates systemic immunity well, but it does not induce sufficient mucosal immunity. Retinoic acid (RA) plays an important role in the induction of cells that imprint gut-homing molecules. We examined whether RA assist parenteral vaccination of pigs could improve mucosal immunity. We demonstrated that elevated numbers of gut-homing CD8+ T cells (which express α4β7 and CCR9 molecules) were presented in porcine inguinal lymph nodes and were recruited to the small intestine by RA. Intestinal mucosal immunity (IgA titre) and systemic immunity (serum IgG titre) were enhanced by RA. Therefore, we hypothesized that RA could induce DCs to form an immature mucosal phenotype and could recruit them to the small intestinal submucosa. Porcine T-cells expressed β7 integrin and CCR9 receptors and migrated to CCL25 by a mechanism that was dependent of activation by RA-pretreated DCs, rather than direct activation by RA. Together, our results provide powerful evidence that RA can assist whole inactivated TGEV (WI-TGEV) via subcutaneous (s.c.) immunization to generate intestinal immunity, and offer new vaccination strategies against TGEV.
Highlights
Immunization subcutanoues route with corn oil subcutanoues route with Retinoic acid (RA) subcutanoues route with WI-transmissible gastroenteritis virus (TGEV) subcutanoues route with RA and whole inactivated TGEV (WI-TGEV) orally immunized with WI-TGEV proliferation[16], up-regulate the expression of gut-homing receptors on lymphocytes, and promote their migration to the intestine[9,10,11,18,20]
To analyze whether RA has the capability of generating gut-homing cells; cells were isolated from the right side of the inguinal lymph nodes (ILNs) and ileum after immunization
The s.c. administration of RA plus TGEV increased the number of gut-homing CD8+ cells expressing β 7-integrin and CCR9 compared with the s.c. administration of TGEV alone in the ILNs (Fig. 1A,B, P < 0.05)
Summary
Immunization subcutanoues route with corn oil subcutanoues route with RA subcutanoues route with WI-TGEV subcutanoues route with RA and WI-TGEV orally immunized with WI-TGEV proliferation[16], up-regulate the expression of gut-homing receptors on lymphocytes, and promote their migration to the intestine[9,10,11,18,20]. Mucosal DCs can augment the expression of integrin α 4β 7 and the chemoattractant receptor, CCR9 on activated lymphocytes in the presence of RA18, which mediates their homing to the gut mucosa[21]. We found that these results will offer new approaches for the development of vaccine candidates against TGEV in newborn piglets
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