The exposure of the lungs to both fungi and non-replicating virus-like particles, elicits immune imprinting to provide exquisite protection against subsequent influenza virus challenge (P3214)

The pulmonary delivery of both virus-like particles (VLPs) (which bear no antigenic similarities to respiratory pathogens), and the opportunistic fungi, Pneumocystis murina, acted to prime the lungs of mice, thus facilitating heightened and accelerated primary immunity to high-dose influenza challenge. These responses were characterized by accelerated antigen processing by alveolar macrophages (AM’s) and dendritic cells (DC’s) and DC trafficking to the local tracheobronchial lymph node (TBLN). Additionally, CD11c+ cells which had been directly exposed to VLPs were necessary in facilitating the observed enhanced viral clearance. The repopulation of CD11c+ DC’s and AM’s from Ly-6Chi myeloid precursors relied on the expression of CCR2, and in the absence of efficient Ly-6Chi cell trafficking in CCR2 knockout mice, or via antibody depletion, the protection afforded by both Pneumocystis- and VLP-exposure was lost. Thus, immune imprinting in the lung by Pneumocystis infection, or VLP-exposure allowed for accelerated influenza-specific primary immune responses in both the lung and TBLN via Ly-6C- or CCR2-dependent mechanisms, respectively. Importantly, both models resulted in enhanced viral clearance and reduced collateral damage.