| Autor: |
Frederick, D R, Goggins, J A, Sabbagh, L M, Freytag, L C, Clements, J D, McLachlan, J B |
| Zdroj: |
Mucosal immunology; March 2018, Vol. 11 Issue: 2 p549-561, 13p |
| Abstrakt: |
Infectious diarrheal diseases are the second leading cause of death in children under 5 years, making vaccines against these diseases a high priority. It is known that certain vaccine adjuvants, chiefly bacterial ADP-ribosylating enterotoxins, can induce mucosal antibodies when delivered parenterally. Based on this, we reasoned vaccine-specific mucosal cellular immunity could be induced via parenteral immunization with these adjuvants. Here, we show that, in contrast to the Toll-like receptor-9 agonist CpG, intradermal immunization with non-toxic double-mutant heat-labile toxin (dmLT) from enterotoxigenic Escherichia colidrove endogenous, antigen-specific CD4+T cells to expand and upregulate the gut-homing integrin α4β7. This was followed by T-cell migration into gut-draining lymph nodes and both small and large intestines. We also found that dmLT produces a balanced T-helper 1 and 17 (Th1 and Th17) response, whereas T cells from CpG immunized mice were predominantly Th1. Immunization with dmLT preferentially engaged CD103+dendritic cells (DCs) compared with CpG, and mice deficient in CD103+DCs were unable to fully license antigen-specific T-cell migration to the intestinal mucosaefollowing parenteral immunization. This work has the potential to redirect the design of existing and next generation vaccines to elicit pathogen-specific immunity in the intestinal tract with non-mucosal immunization. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
Full text from SpringerLink