Intranasal immunization with polymer-grafted microparticles activates the nasal-associated lymphoid tissue and draining lymph nodes

Abstract

Waldeyer's ring is located at the juncture of the respiratory and alimentary tracts, where it is bombarded by inhaled and ingested antigens. However, knowledge of its exact function or consequences of its removal is incomplete. Recently, the murine nasal-associated lymphoid tissue (NALT) has been reported to have functional similarities to Waldeyer's ring and, thus, might be a suitable model to examine the function of oronasopharyngeal lymphoid tissues. To explore the capability of NALT to incite local mucosal and systemic immunity, we immunized mice intranasally (i.n.) with 3-(triethoxysilyl)-propyl-terminated polydimethylsiloxane (TS-PDMS)-grafted microparticles (MP), an inoculant previously shown to induce robust systemic and mucosal humoral immunity following intragastric (i.g.) administration. We demonstrated that i.n. immunization with low doses of microentrapped, but not soluble, human serum albumin (HSA) evoked robust circulating IgG responses (P < 0.05). Additionally, NALT cells isolated from MP-treated mice proliferated in vitro when restimulated with HSA (P < 0.05), suggesting that i.n. immunization with HSA-containing MP incited specific immunity via NALT cell activation. Coinciding with these observations, after i.n. MP administration HSA-specific spot-forming cells (SFC) were observed in NALT, and later posterior cervical lymph nodes (pCLN) and spleen (SPL), suggesting that the observed MP-induced specific systemic antibody responses emanated from the NALT. We also showed that i.n. immunization with HSA-containing TS-PDMS-grafted MP stimulated interleukin-4 (IL-4)-secreting lymphocytes in the NALT. This cytokine microenvironment was probably responsible for driving the IgG1 sera response observed after i.n. MP administration, via the migration of NALT-derived IgG1-committed B cells. Interestingly, unlike i.g. MP administration, i.n. immunization with HSA-containing MP did not evoke detectable specific IgA in any lymphoid tissue examined, or in nasal secretions, probably reflecting differences between NALT and other mucosae-associated lymphoid tissues (MALT).