Allergoid-mannan conjugates imprint tolerogenic features in human macrophages

Abstract

Allergen-specific immunotherapy (AIT) is the only treatment for allergic diseases with potential curative capacity. Successful AIT is associated with the induction of functional allergen-specific Tregs, Bregs, and blocking IgG antibodies. AIT also restores the levels and composition of circulating innate immune cells to those observed in healthy individuals. Polymerized allergoid-mannan conjugates (PM) are novel AIT vaccines being currently assayed in phase II clinical trials. PM target dendritic cells (DCs) and generate functional FOXP3+ Tregs in vitro and in vivo, which is impaired by alum. We recently demonstrated that PM reprogram monocytes from healthy donors and allergic patients into tolerogenic DCs via epigenetic and metabolic reprogramming. However, their capacity to regulate macrophage polarization remains unknown. Macrophages (MØ) exhibit sufficient cell plasticity to be able to polarize into different phenotypes, from pro-inflammatory, pathogen-eliminating, and subsequent tissue-damaging to anti-inflammatory or more regulatory profiles. Together with other innate immune cells, MØ play a key role in tolerance induction during AIT.