Probing local innate immune responses after mucosal immunisation.

Abstract

BACKGROUND: Intranasal immunisation is potentially a very effective route for inducing both mucosal and systemic immunity to an infectious agent. METHODS: Balb/c mice were intranasally immunised with the mucosal adjuvant heat labile toxin and the Mycobacterium tuberculosis fusion protein Ag85B-ESAT6 and early changes in innate immune responses within local mucosal tissues were examined using flow cytometry and confocal microscopy. Antigen-specific humoral and cellular immune responses were also evaluated. RESULTS: Intranasal immunisation induced significant changes in both number and distribution of dendritic cells, macrophages and neutrophils within the nasal-associated lymphoid tissue and cervical lymph nodes in comparison to controls as early as 5 h post immunisation. Immunisation also resulted in a rapid and transient increase in activation marker expression first in the nasal-associated lymphoid tissue, and then in the cervical lymph nodes. This heightened activation status was also apparent from the pro-inflammatory cytokine profiles of these innate populations. In addition we also showed increased expression and distribution of a number of different cell adhesion molecules early after intranasal immunisation within these lymphoid tissues. These observed early changes correlated with the induction of a TH1 type immune response. CONCLUSIONS: These data provide insights into the complex nature of innate immune responses induced following intranasal immunisation within the upper respiratory tract, and may help clarify the concepts and provide the tools that are needed to exploit the full potential of mucosal vaccines.