Nonmucosal alphavirus vaccination stimulates a mucosal inductive environment in the peripheral draining lymph node.
Publication/Presentation Date
7-1-2008
Abstract
The strongest mucosal immune responses are induced following mucosal Ag delivery and processing in the mucosal lymphoid tissues, and much is known regarding the immunological parameters which regulate immune induction via this pathway. Recently, experimental systems have been identified in which mucosal immune responses are induced following nonmucosal Ag delivery. One such system, footpad delivery of Venezuelan equine encephalitis virus replicon particles (VRP), led to the local production of IgA Abs directed against both expressed and codelivered Ags at multiple mucosal surfaces in mice. In contrast to the mucosal delivery pathway, little is known regarding the lymphoid structures and immunological components that are responsible for mucosal immune induction following nonmucosal delivery. In this study, we have used footpad delivery of VRP to probe the constituents of this alternative pathway for mucosal immune induction. Following nonmucosal VRP delivery, J chain-containing, polymeric IgA Abs were detected in the peripheral draining lymph node (DLN), at a time before IgA detection at mucosal surfaces. Further analysis of the VRP DLN revealed up-regulated alpha4beta7 integrin expression on DLN B cells, expression of mucosal addressin cell adhesion molecule 1 on the DLN high endothelia venules, and production of IL-6 and CC chemokines, all characteristics of mucosal lymphoid tissues. Taken together, these results implicate the peripheral DLN as an integral component of an alternative pathway for mucosal immune induction. A further understanding of the critical immunological and viral components of this pathway may significantly improve both our knowledge of viral-induced immunity and the efficacy of viral-based vaccines.
Volume
181
Issue
1
First Page
574
Last Page
585
ISSN
0022-1767
Published In/Presented At
Thompson, J. M., Nicholson, M. G., Whitmore, A. C., Zamora, M., West, A., Iwasaki, A., Staats, H. F., & Johnston, R. E. (2008). Nonmucosal alphavirus vaccination stimulates a mucosal inductive environment in the peripheral draining lymph node. Journal of immunology (Baltimore, Md. : 1950), 181(1), 574–585. https://doi.org/10.4049/jimmunol.181.1.574
Disciplines
Medicine and Health Sciences
PubMedID
18566424
Department(s)
Fellows and Residents
Document Type
Article