The immune system is formed by cells and tissues tightly integrated with other systems of the organism. An example of this crosstalk between different systems is represented by the well-known fact that the immune system takes advantage of the blood system to distribute its cells in every compartment of the host. We investigated the crosstalk between the immune system and the fibrinolytic system (Science immunology, 2017). Using a mouse model deficient in NFAT to examine the response to Candida albicans fungal infection, this study showed two distinct phases of the immune response. First, an abscess forms to contain the pathogen; then, ulceration in the skin occurs, which facilitates the expulsion of the pathogen from the tissue. Abscess formation is reliant on transforming growth factor-β (TGFβ), a pro-fibrotic signal. Importantly, the second ulceration phase does not occur in NFAT-deficient animals, suggesting that the ‘switch’ between phases might rely on attenuating TGFβ activity. The study demonstrated that dendritic cells express NFAT; this expression is required for interleukin-2 secretion that, in turn, promotes interferon-γ production by NK cells. Interferon-γ then blocks the TGFβ-mediated pro-fibrotic containment of the pathogen (abscess formation) and regulates the fibrinolytic ulcerative program that leads to abscess clearance. These data suggest the possibility of applying interferon-γ therapeutically in the context of fibrotic pathologies and further increase understanding of the complex interactions between the immune system and other systems of the host.

We are currently investigating how specific components of the fungal cell wall dictate the activation of the immune response and how fungal ligands can be exploited to mount sterilizing anti-fungal responses.

ZanoniLab

Murine bone marrow-derived macrophages stimulated with microbial ligands for 24 hours. Actin cytoskeleton and nuclei were stained with Alexa Fluor® 488 conjugated phalloidin (pseudo-color green) and DAPI (pseudo-color blue) respectively. Activated macrophages produce filopodia necessary for their anti-microbial responses. Credit: Marco Di Gioia

Header picture: Murine bone marrow-derived macrophages were stimulated with microbial ligands and cellular ultrastructures were analyzed by electron microscopy. Credit: Marco Di Gioia