Activation of innate immune cells by PRR ligands is a critical step for the initiation of the adaptive immune response. The cellular and molecular events triggered by PRR-mediated activation of innate immune cells allowed the identification of signaling organelles, metabolic pathways and gene expression profiles that shape the innate immune response. However, cell-intrinsic features of PRR activation and signaling are not sufficient to explain the complexity of the in vivo inflammatory response elicited by innate stimuli. Indeed, their localization at cellular and organismal levels plays a key role in determining the activation status of innate immune cells. In light of these consideration, we hypothesize that the physical properties (e.g. solubility and diameter) of PRR ligands have a critical impact on modulating tissues targeting and innate immune activation profiles.

We are currently investigating how specific components of Candida albicans fungal cell wall dictate the activation of the immune response and how the physical properties of fungal ligands, in particular, or other PAMPs, in general, can be exploited to initiate unique innate signaling pathways that may impact not only the extent, but also the quality of the adaptive immune response. In particular, we aim at expanding T and B cell immunodominance to create more efficient vaccine adjuvants.

ZanoniLab

Confocal microscopy of the draining lymph node of a mouse injected with fungal ligand in the skin. Red: B cells; Green: mannans; White: phospho Syk; Blue: nuclei. Credit to Dr. Borriello

Header picture: Confocal microscopy of the draining lymph node of a mouse injected with fungal ligand in the skin. Blue: nuclei; White: B cells; Red: subcapsular macrophages; Green: mannans. Credit to Dr. Borriello