Pentraxin 3 protects from Aspergillus infection and inflammation in chronic granulomatous diseases

Zelante T., De Luca A., D Angelo C., Romani L.

Author address: 

NULL

Abstract: 

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by life threatening bacterial and fungal infections. However, CGD patients not only suffer from recurrent infections, but also present with inflammatory, non-infectious conditions. The susceptibility of CGD mice to aspergillosis is associated with the failure to control the inherent inflammatory response to the fungus and to restrict the activation of inflammatory Th 17 cells, a finding suggesting that unrestricted Th 17 cell activation is a general mechanism underlying hyperinflammation in condition of NADPH deficiency. We found that exogenous administration of PTX3 inhibited the local fungal growth and dissemination to distal organs and restrained the inflammatory response to A. fumigatus in CGD mice. This occurred through down regulation of IL23 production by dendritic cells and epithelial cells, which resulted in limited expansion of IL23R+ gamma delta+ T cells producing IL17 A and the emergency of Thl/Treg responses to the fungus with minimum pathology. PTX3 worked synergistically with voriconazole to restrict the fungal growth and decrease the lung inflammatory response. This study suggests that the NADPH independent mechanism(s) of antifungal immune protection are amenable to manipulation in CGD and that PTX3 could be successfully exploited as a novel therapeutic agent with anti-inflammatory properties.
2009

abstract No: 

PP-02-6

Full conference title: 

17th International Society for Human and Animal Mycology
    • ISHAM 17th (2009)